US President Donald Trump said "everyone should immediately evacuate Tehran" in a post on his Truth Social platform on Monday.
It is unclear why Mr Trump made the demand about a city of about 10 million residents, but a White House official told CNN that it reflected the urgency of the need for Iran to come to the negotiating table.
"Iran should have signed the 'deal' I told them to sign. What a shame, and waste of human life," he wrote.
The President was referring to continuing talks aimed at developing a new deal between the US and Iran that would put limits on Tehran's nuclear programme in return for sanctions relief. Iran has insisted that its nuclear work is for peaceful purposes.
In a separate post, Mr Trump said: "America First means many great things, including the fact that Iran cannot have a nuclear weapon. Make America great again."
Israel said its actions were aimed at ensuring Iran does not develop a nuclear weapon – something Israeli officials have claimed it was only days away from.
The talks, which Mr Trump has accused Iran of "slow-walking", have stalled amid the conflict.
Mr Trump is at the G7 summit in Alberta, Canada, where discussions have focused on the Israel-Iran conflict. But White House press secretary Karoline Leavitt said in a post to Truth Social that Mr Trump would return to Washington on Monday night "because of what’s going on in the Middle East".
Not long after Mr Trump's post on Truth Social, Iran's Islamic Revolutionary Guard Corps posted a map on its Telegram channel showing the locations of US military bases and what appeared to be the number of troops in the Middle East.
This is the fourth day of aerial strikes by both countries, after Israel launched a "pre-emptive" attack on Tehran last week.
The President's comments came as Israel reportedly engaged in a renewed attack on Tehran, with officials saying it would go "launcher by launcher" to destroy Iran's missile strength.
Iran fired hundreds of missiles back, hitting a power plant in Haifa and destroying buildings in Tel Aviv.
Earlier on Monday, Israel proclaimed "aerial superiority" over Iran and attacked a state-run broadcaster, killing at least one person, according to reports.
The US has been adamant that it was not involved in Israel's decision to strike Iran. But Mr Trump said on Sunday that it is "possible we could get involved".
US Defence Secretary Pete Hegseth said on Monday that he had ordered more defensive assets to be sent to the Middle East. While he did not detail what assets had been moved, Reuters reported that a large number of US military refuelling aircraft and a carrier were heading to the region.
"Protecting US forces is our top priority and these deployments are intended to enhance our defensive posture in the region," Mr Hegseth said in a post on X.
