"Let me say tonight if you are watching television in Iran," Graham said on "Hannity." " I just got off the phone with the president. Your fate is in your own hands in terms of the regime's economic viability."
Iran fired 15 ballistic missiles that targeted two Iraqi airbases housing U.S. and coalition forces, a major act of retaliation by the rogue regime after the death of Quds Force Gen. Qassem Soleimani last week.
"This was an act of war," Graham continued. "By any reasonable definition. The missiles were launched from Iran. The president has all the authority he needs under Article II to respond. It was an act of war by the regime that for the last 40 years has been a cancer in the Mideast. When they say they want to destroy Israel, they are not kidding," he continued.
Graham, a member of the Senate Foreign Relations Committee, expressed confidence that Trump would take appropriate action in due time.
"The president has to do a couple things tonight," Graham said. "What can I do to restore deterrence to make sure this doesn't happen again? He doesn't want regime change. He wants the behavior of the regime to change in three areas: Their ballistic missile program needs to change, they need to stop being the largest state sponsor of terrorism, and we need a nuclear deal that does not ensure them a pathway to a bomb like Obama."
"Obama was kind by the Iranians -- Trump is not going to be kind," he added.
Graham further praised the president for ordering the U.S. airstrike that killed Soleimani last week.
"We are dealing with religious Nazis. They have been disrupting the Mideast for 40 years...," he said. "Here's what the president, I think understands about the Iranians. They are never going to change until you make them change. For the last 40 years, they have been wreaking havoc on the world and we’ve got a new sheriff in town."
Expressing gratitude to U.S. troops currently deployed in the Middle East, Graham said they act as "a virtual wall between us and radical Islam," and assured their families that the president will prioritize their safety.
"I want to ... thank those that are serving in uniform in the Mideast. You are the virtual wall between us and radical Islam," Graham said.
"We can build a wall along our southern border to protect us there, but you can't build a wall between us and radical Islam. You need some of our people working with others to keep these bastards at bay."
" I have complete confidence in President Trump and his team to protect your family members and to protect our nation," he added.
"This is the first president in the last 40 years who really understands the Iranians."
Fox News' Frank Miles contributed to this report.