The White House has said they are working on evacuation flights and cruise ship departures for American citizens in Israel.
Mike Huckabee, the US Ambassador in Israel, has confirmed that the options are currently voluntary.
It comes amid a rise in tensions between Iran and Israel as the conflict between the two countries escalates.
After Ayatollah Ali Khamenei rejected Donald Trump's demand for unconditional surrender, the President declined to say whether he had made any decision on whether to join Israel's bombing campaign against Iran.
President Trump has ordered the evacuation
REUTERS
People evacuated from Israel disembark from a plane, amid the Israel-Iran conflict in Sofia, Bulgaria
REUTERS
Trump said: "I may do it. I may not do it. I mean, nobody knows what I'm going to do."
Asked for his response to Khamenei rejecting his demand to surrender, President Trump said: "I say, good luck."
Khamenei, 86, rebuked Trump in a recorded speech played on television, his first appearance since Friday.
The Americans "should know that any US military intervention will undoubtedly be accompanied by irreparable damage," he said.
"Intelligent people who know Iran, the Iranian nation and its history will never speak to this nation in threatening language because the Iranian nation will not surrender."
LATEST DEVELOPMENTS FROM TEHRAN
Smoke rises following an Israeli attack in Tehran, Iran
REUTERS
A Home Front Command Israeli soldier stands next to damaged residential buildings following missile attack from Iran to Israel
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Traffic was backed up on highways leading out of the capital Tehran, a city of 10 million people, as residents sought sanctuary elsewhere.
Arezou, a 31-year-old Tehran resident, told reporters by phone that she had made it out to the nearby resort town of Lavasan.
"We will stay here as long as this war continues. My friend’s house in Tehran was attacked and her brother was injured. They are civilians," she said. "Why are we paying the price for the regime’s decision to pursue a nuclear programme?”
In Israel, sirens rang out warning people of retaliatory Iranian missile strikes.
At Ramat Gan city train station east of Tel Aviv, people were lying on city-supplied mattresses lined along the floor or sitting in the odd camping chair, with plastic water bottles strewn about.
Rescuers work at the site of a damaged building, in the aftermath of Israeli strike
REUTERS
Iranian officials have reported at least 224 deaths in Israeli attacks, mostly civilians, though that toll has not been updated for days.
In Israel, Iran's missile volleys mark the first time in decades of shadow war and proxy conflict that a significant number of projectiles fired from Iran have penetrated defences, killing Israelis in their homes.
Since Friday, Iran has fired around 400 missiles at Israel, some 40 of which have pierced through air defences, killing 24 people, all of them civilians, according to Israeli authorities.
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