Khamenei also made threatening comments aimed at Trump, saying he's made a big mistake and Trump will be "worm food" while the Iranian republic is still standing.
Trump this week called the agreement "disastrous," and promised the "highest level of economic sanctions against Iran."
But longer term, analysts also say the bigger issue is the schism in Iranian internal politics, and who ultimately gains the upper hand.
"Rouhani doesn't control the nuclear field. The supreme leader does. What does the supreme leader do now? I think the biggest risk is the hard-liners in Iran get the upper hand, and Iran resumes their nuclear program. I think Rouhani may have been discredited today," said Helima Croft, global head of commodity strategy at RBC Capital Markets.
As analysts assess what impact renewed sanctions may have, they point to the fact that China is unlikely to curtail its purchases of Iranian oil, and may in fact increase them. Iran is also likely to find an ally in Russia, also under U.S. sanctions.
Iran could first explore diplomatic channels after Trump's decision to resume sanctions on the country based on evidence from Israel that Iran is continuing a nuclear program and its support of terrorist organizations in the Middle East. But while it could go to the United Nations General Assembly, the U.S. sits on the Security Council.
U.N. Secretary-General Antonio Guterres said he was deeply concerned by the U.S. action.
Analysts expect European companies that do not want to be prohibited from dealing with the U.S. to comply with the renewed sanctions, but European leaders are expected to continue to work to find a way to keep the pact in place.
"While there is considerable debate over the effectiveness of unilateral U.S. action on Iran, we think that a revival of the threat to lock noncompliant corporates out of U.S. capital markets provides the White House with a pretty powerful stick," notes Croft. "While Chinese compliance is probably a nonstarter, we do anticipate a high degree of cooperation from European, Japanese and South Korean corporates despite their host government's opposition to the U.S. move."
French President Emmanuel Macron tweeted that there will be a continued effort to work on a broader framework to include lengthening the nuclear agreement and curbing ballistic missiles and Iranian activity in Yemen and Syria.
Carlos Pascual, a former U.S. diplomat and the State Department's top energy official when the sanctions were first imposed, said one way forward could be a parallel set of sanctions that the U.S. could agree to with Europe on the topics mentioned by Macron.
"I imagine what will happen is the administration will continue some form of discussion or dialogue with the Europeans on whether there are supplementary sanctions that could be put in place on ballistic missiles. It's unclear what might be done to constrain Iran in the region," said Pascual, a senior vice president at IHS Markit.
He said Iran's activity in the region extends to Hezbollah and Hamas, and into places like Syria, Libya, Lebanon and Yemen.
"Sanctions on Iran's involvement in the region become complicated because they are so extensive, and they are hard to measure and verify. It would be extremely difficult to implement," said Pascual.
According to U.S. and allied intelligence, there are an estimated 40,000 Iranian troops and militia on the ground in Syria, and as many as 2,500 Iranians, including high-ranking generals, have been killed there.
"There's no question that Iran's regional behavior has been intrusive and self interested as they've tried to deepen and expand their involvement in Syria to be able to advance Iranian interests, in particular to make sure they maintain a direct linkage to Hezbollah in Lebanon," Pascual said. "That's their principle mechanism of wreaking havoc on Israel."
Iran learned to get around sanctions the last time, and it could do so again but more successfully, analysts said. Instead of the more than 1 million barrels a day that were kept off the market in the last round of sanctions, the result is likely to be somewhere between 300,000 and 500,000, since U.S. allies do not support ending the deal, known as the Joint Comprehensive Plan of Action.