Thursday is the first full day of President Biden's administration and with it he and Vice President Harris will face a litany of challenges both at home and abroad, and the reality that they are no longer on the campaign trail or in transition -- they are the leaders of the free world. 

The stakes are extraordinarily high -- Biden, at age 78, now has a job notorious for aging those who hold it. The physical aging over eight years in his former running mate, President Obama, was stark, as was that for former President George W. Bush. 

From establishing a functioning White House and redirecting executive agencies to carry out their visions, to dealing with menacing threats abroad, Biden and Harris face a number of obstacles.

Here are the top challenges Biden and Harris face on their first full day in office. 

Coronavirus pandemic and vaccines

The biggest challenge that faced the Trump administration in its final year is not going away for the Biden administration. He acknowledged that in his inaugural address, calling for a moment of silence for those killed by the virus.

President Joe Biden speaks during the 59th Presidential Inauguration at the U.S. Capitol in Washington, Wednesday, Jan. 20, 2021.(AP Photo/Patrick Semansky, Pool)

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More than 400,000 Americans have died from the virus and many businesses remain unable to fully open due to state government guidelines. Millions of Americans are still forced to work from home, and many others are unemployed. 

With state governments eager to receive more doses of the various coronavirus vaccines, Biden will have to find a way to speed up what has been a lagging rollout of the United States' vaccine program. 

Biden promised that his administration will get "at least 100 million COVID vaccine shots into the arms of the American people in the first 100 days." That will be a heavy lift. 

Further, Biden recently rolled out an ambitious $1.9 trillion coronavirus package that he hopes to pass through Congress. Punchbowl News reported Wednesday that lawmakers are not sure they'll be able to get that legislation to his desk until March. 

That will only be the case, of course, if enough Republicans in the Senate decide not to filibuster the package. They wouldn't give Trump the $2,000 coronavirus relief checks he sought, citing concerns about government spending. 

Thin margins in Congress

Thin margins in Congress won't just color Biden's efforts to pass coronavirus relief, but just about everything he will do that touches the legislature.

Kamala Harris is sworn in as vice president by Supreme Court Justice Sonia Sotomayor as her husband Doug Emhoff holds the Bible during the 59th Presidential Inauguration at the U.S. Capitol in Washington, Wednesday, Jan. 20, 2021. ((Saul Loeb/Pool Photo via AP))

That means executive nominations, judicial nominations, government funding, national security and more. 

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Republicans picked up seats in the House during the November elections, shrinking the Democrat majority to what will be approximately a 10-seat advantage for the next two years.

That means Democrats can afford very few defections on major votes. 

House Majority Leader Steny Hoyer, D-Md., in December said that he was "certainly concerned" by some of Biden's appointments of Democrat House members into his administration, thus slimming the Democrat majority even further. But he added that he believes Democrats will "be a very unified caucus as we were this past Congress" and be able to pass Biden's agenda items. 

In the Senate, Democrats picked up enough seats to gain what will be a de facto majority with 50 senators for each party and Harris able to break ties on votes that fall along party lines. She'll have to be significantly more involved in the Senate's affairs than most recent vice presidents for this reason. 

The filibuster is likely to be a significant issue. Republicans will be able to block many items from passing in the Senate by withholding their support on cloture votes, which are procedural hurdles required to get to a final vote on a bill, and require 60 votes to pass.

Senate Minority Leader Mitch McConnell (R-KY) arrives at the U.S. Capitol on January 1, 2021 in Washington, DC. The Senate is scheduled to convene today to resume consideration to potentially override President Trump’s veto of the National Defense Authorization Act. (Photo by Liz Lynch/Getty Images)

Power-sharing negotiations between Majority Leader Chuck Schumer, D-N.Y., and Minority Leader Mitch McConnell, R-Ky., were snagged this week as McConnell attempted to extract assurances that Democrats won't get rid of the filibuster. 

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"During today’s meeting, Leader McConnell expressed his long-held view that the crucial, longstanding, and bipartisan Senate rules concerning the legislative filibuster remain intact, specifically during the power share for the next two years," McConnell spokesman Doug Andres said on Tuesday. "Discussions on all aspects of the power-sharing agreement will continue over the next several days."

Building an administration 

Biden during his transition already made a number of choices for his White House staff, with Chief of Staff Ron Klain and Press Secretary Jen Psaki among the highest-profile. 

But a president is not just in charge of the White House but also the entire executive branch. That means Biden will also need to fill key national security and domestic Cabinet positions while also turning around staff at lower levels of executive agencies and steering them in the direction of his administration's policy. 

Ron Klain, former White House Ebola response coordinator, speaks during a House Homeland Security Subcommittee hearing in Washington, D.C., U.S., on Tuesday, March 10, 2020. Klain is President Biden's White House chief of staff. Photographer: Andrew Harrer/Bloomberg via Getty Images

One of Biden's first actions is placing Department of Justice employee Monty Wilkinson in as acting attorney general, in place of Rod Rosenstein, who Trump selected as acting attorney general. Wilkinson will serve in the role until D.C. Circuit Court Judge Merrick Garland is confirmed by the Senate as attorney general. 

The Senate is expected to confirm a handful of Biden's other Cabinet picks immediately, likely including Janet Yellen, his pick for Treasury secretary. It signed off on Director of National Intelligence Avril Haines Wednesday. 

One obstacle to this effort, however, is the upcoming impeachment trial for Trump, which may end with him being disqualified from holding office in the future. 

House Speaker Nancy Pelosi, D-Calif., hasn't yet sent the article of impeachment, accusing Trump of inciting an insurrection, to the Senate. This is likely to allow the Senate to quickly move on some of Biden's less controversial cabinet appointments before it's forced to take up the impeachment trial. 

Biden previously suggested that the Senate could "go a half-day on dealing with impeachment, a half-day on getting my people nominated and confirmed in the Senate, as well as moving on the [Biden coronavirus] package." But that would require an agreement from McConnell and Schumer, which has not yet materialized. 

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Debt and deficit

Trump leaves Biden with a hulking $27.8 trillion national debt after ballooning deficits and the debt even more than Obama did. 

Now, with the pandemic still raging, Biden plans to spend even more on coronavirus relief while also planning for expensive initiatives on the climate and more. 

Senate Minority Leader Mitch McConnell of Ky., listens as Sen. John Thune, R-S.D., speaks during a news conference with other Senate Republicans on Capitol Hill in Washington, Tuesday, Dec. 15, 2020. (Rod Lamkey/Pool via AP)

While Democrats are traditionally not concerned about deficit spending, Republicans have telegraphed that they will put a renewed emphasis on the issue during the Biden administration. 

Senate Republican Whip John Thune, R-S.D., told The Hill in November that that cutting spending is "kind of getting back to our DNA... I would expect you'll hear a lot more about that." He also warned that he hopes the next president realizes "how serious the debt crisis is and how important it is that we put measures in place to address it."

Addressing GOP deficit concerns could be key to Biden getting some of his larger agenda items passed. 

China and Russia

After a campaign in which Biden was hammered on his son Hunter's alleged business ties to China -- and four years in which Trump was hammered for being Russia's preferred candidate in the 2016 election -- the reality is that the two authoritarian countries remain significant threats to American interests. 

A months-long cyberattack by Russia on the U.S. was recently discovered, the extent of which is still likely not fully understood.

China is a threat to the United States economically, militarily in the South China Sea, in space, and in the Arctic. It's also a global human rights threat -- the State Department earlier this week declared China to be committing genocide in its persecution of the Uyghur Muslims. 

In this photo released by China's Xinhua News Agency, Chinese President Xi Jinping, left, Premier Li Keqiang, second from left, and other top leaders attend a New Year gathering hosted by the Chinese People's Political Consultative Conference (CPPCC) in Beijing, Thursday, Dec. 31, 2020. (Yao Dawei/Xinhua via AP)

Biden's incoming secretary of state, Anthony Blinken, indicated in a confirmation hearing Tuesday that the Biden administration will keep up the Trump administration's tough stance on China. 

"President Trump was right in taking a tougher approach to China," said Blinken, who served as then-Vice President Biden’s national security adviser before being elevated to deputy secretary of state under Obama. "Not the way he went about it in a number of ways, but the basic principle was right." 

Immigration and impending migrant caravan

Biden has promised to implement massive immigration reform, including a path to citizenship for 11 million illegal immigrants. 

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"I’ve made it very clear, within 100 days, I’m going to send to the United States Congress a pathway to citizenship for over 11 million undocumented people," Biden said in the second presidential debate. "And all those so-called Dreamers, those DACA kids, they’re going to be immediately certified again, to be able to stay in this country, and put on a path to citizenship."

It's not clear this will be possible in Biden's first 100 days, but during that time Biden will be forced to deal with a migrant caravan moving to America's border from Central America. 

On Friday, two groups of more than 3,000 Honduran migrants each pushed their way into Guatemala without registering as part of a larger caravan headed to the United States, the Associated Press reported. A third group entered Guatemala on Saturday. The migrants aim to reach Mexico and eventually make their way to the United States border. 

Biden's nominee to lead the Department of Homeland Security, Alejandro Mayorkas, was pressed on how he would handle the caravan during a confirmation hearing Tuesday by Sen. Mitt Romney, R-Utah.

"What is your intention with regards to that caravan, that is coming to our border. Is your intention to allow them just to come into our country? Will they be stopped?" Romney asked. 

Honduran migrants clash with Guatemalan soldiers in Vado Hondo, Guatemala, Sunday, Jan. 17, 2021. Guatemalan authorities estimated that as many as 9,000 Honduran migrants crossed into Guatemala as part of an effort to form a new caravan to reach the U.S. border. (AP Photo/Sandra Sebastian) (AP)

"When people present themselves at our border, we apply the laws of our nation and determine whether they qualify for relief under our humanitarian laws or whether they don't," Mayorkas said. 

Romney responded that his answer appeared "uncertain." 

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"I apologize if I was uncertain. If people qualify under the law to remain in the United States, then we will apply the law accordingly. If they do not qualify to remain in the United States, then they won't," Mayorkas said. 

Sharply divided country

With stark divisions among not just those in Congress but American citizens in general, Biden faces the herculean task of healing a nation where citizens not only don't trust the government, but often don't trust each other. 

Biden addressed this task during his inauguration speech. 

"We must end this uncivil war that pits red against blue, rural versus urban, conservative versus liberal," Biden said. 

He added: "With purpose and resolve we turn to the tasks of our time, sustained by faith, driven by conviction, devoted to one another and the country we love with all our hearts."

Despite the fact that more than 100 House Republicans voted against certifying his election, he may have some help from a group of House freshmen Republicans. 

"After two impeachments, lengthy inter-branch investigations, and, most recently, the horrific attack on our nation’s capital, it is clear that the partisan divide between Democrats and Republicans does not serve a single American,'" said the group, which includes Reps. Jerry Carl, R-Ala.; Barry Moore, R-Ala.; Young Kim, R-Calif.; Peter Meijer, R-Mich.; Madison Cawthorn, R-N.C.; and others. 

It continues: "We firmly believe that what unites us as Americans is far greater than anything that may ever divide us. In that spirit, we hope that we can rise above the partisan fray to negotiate meaningful change for Americans across the nation and maintain the United States’ standing as the best country in the world."

Far-left of Democratic Party

Rep. Alexandria Ocasio-Cortez saw that Congress is "looking into" media literacy initiatives to help "rein in" the press to combat misinformation in the wake of last week’s deadly breach of the U.S. Capitol. (Photographer: Tom Williams/CQ Roll Call/Bloomberg via Getty Images) (Getty Images)

Biden won't only have to grapple with GOP resistance to his agenda, but with the left wing of his own party that wants to push him to be more ambitious. 

Rep. Alexandria Ocasio-Cortez, D-N.Y., this week said that she disagrees with Biden's "optimistic" view that he can work with Republicans. 

"This is one area where I believe that there's kind of a track record of some slight disagreement between the president-elect and myself, and I say that, you know -- this is it, it's not a fight - it's just a disagreement," she said in a virtual town hall. "I believe that President-elect Biden has a very optimistic view of the Republican Party. He, he has made statements on, you know, once Trump is gone, they will see the error of their ways. And I applaud his optimism but I disagree with his assessment."

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Ocasio-Cortez is the figurehead for "The Squad" of progressive Democrats in the House, and her mini-caucus just got bigger this year. Reps. Cori Bush, D-Mo., and Jamaal Bowman, D-N.Y., defeated moderate Democrats in primaries last year and figure to be vocal members of the House in the next year. 

Energy and climate change 

One of the priority issues for those "Squad" members is significant action on climate change. Biden has staked out a more moderate position. 

Among the stances on climate that Biden has taken is one to "transition from the oil industry" without banning fracking -- upsetting both those on the right and the left. 

Biden also turned heads earlier this week when he announced his plan to kill the Keystone XL oil pipeline. This upset a number of Republicans from energy-rich states, including Rep Matt Rosendale. R-Mont. 

"America's energy sector is important to our economy and critical to our national security by helping make us energy independent," he said in a statement Tuesday. "This pipeline means a lot for our country and Montana. As we are in the midst of great economic uncertainty, I encourage President-elect Biden to reverse his proposed decision to cancel the Keystone XL Pipeline and the thousands of good-paying jobs it will provide."

Fox News' David Spunt, Mike Emanuel, Morgan Phillips and The Associated Press contributed to this report.