Though the CIA and an agency under the Director of National Intelligence have been under particular scrutiny in the preliminary review of possible missteps, Napolitano so far has taken the most heat from lawmakers. Not only does her department oversee the Transportation Security Administration, but her initial claim Sunday that "the system worked" was widely ridiculed and interpreted by critics as a sign that she's in over her head.
Some Republicans, who've taken issue with her in the past for calling terrorist acts "man-caused disasters" and other remarks, started calling for her ouster in the spring. The failed bombing on Christmas Day revived those calls.
Now Democrats have joined the chorus.
New Jersey State Senate President Richard Codey, a Democrat, wrote a letter to Napolitano this week calling on her to step down. He said Napolitano, an attorney and former Arizona governor, does not have the experience for the post she is in.
"We should have someone who doesn't need to go in there and learn about terrorism, learn about security," Codey told Fox News. "How close were these 300 people on this plane from losing their lives because homeland security broke down? Boy, it was really close."
The Department of Homeland Security was created in the wake of the Sept. 11, 2001, terror attacks and has grown into one of the largest Cabinet departments in the federal government. Charged with keeping the nation safe from terrorist attacks and responding to natural disasters, it covers the TSA, the Federal Emergency Management Agency, Immigration and Customs Enforcement and a slew of other agencies.
Codey said a candidate "well-versed" in intelligence should step into the job.
Democratic strategist Dan Gerstein also said Napolitano's response to the incident should be the last straw.
"I tend to think she will be pushed out in the next couple of months," Gerstein, a former adviser to Sen. Joe Lieberman, I-Conn., said.
For now, the administration says it has absolute confidence in Napolitano. She is an active part of the internal review and on Thursday took additional steps to improve security at international airports.
She announced that she's sending senior officials abroad to meet with leaders from international airports to review security measures. Napolitano said she is "fully committed to making whatever changes are necessary to protect the safety of the traveling public."
Napolitano on Monday also clarified that she didn't believe "the system worked" in the run-up to the attempted bombing, which failed because the explosive mixture used did not properly detonate. Napolitano said she was merely referring to the inter-agency cooperation in the aftermath of the attempt.
To Republicans who have lambasted the administration in recent days over its response, the White House accuses critics of playing political games.
"Unfortunately too many are engaged in the typical Washington game of pointing fingers and making political hay, instead of working together to find solutions to make our country safer," Communications Director Dan Pfeiffer wrote on the White House blog.
Republicans, though, have not held back.
Republican Rep. Dan Burton, R-Ind., said Napolitano does not have the experience for the job, and her remarks only prove that she doesn't take the terrorist threat as seriously as she should.
"She's not doing her job," Burton told Fox News.
Former New York Republican Sen. Alfonse D'Amato also said Napolitano should resign.
But other Democrats are urging lawmakers not to jump to conclusions when the internal review is only now getting underway.
Rep. Bill Pascrell, D-N.J., said that if it turns out the secretary dropped the ball then members of Congress will ask for her resignation.
"I'm not at that point yet," he said.