Some are calling it the strongest speech ever by a secretary of state.
In his first major foreign policy address, Mike Pompeo focused on Iran, warning leaders to change course or face their strongest sanctions in history.
"Sanctions are going back in full effect, and new ones are coming," Pompeo said, speaking at the Heritage Foundation, a conservative think tank.
Pompeo said he will also be working with the Defense Department and allies to push back on Iran.
"We will ensure freedom of navigation on the waters in the region. We will work to prevent and counteract any Iranian malign cyber activity. We will track down Iranian operatives and their Hezbollah proxies operating around the world and crush them," Pompeo said. "Iran will never again have carte blanche to dominate the Middle East."
Pompeo listed twelve demands that would be the framework for a potential new treaty with Iran.
Pompeo said Iran must fully disclose and permanently abandon its nuclear weapons program.
It must also end its ballistic missile program and allow inspectors access to all nuclear sites, including the military locations which were off limits under the 2015 deal.
"Iran must release all US citizens as well as citizens of our partners and allies, each of them detained on spurious charges," he said.
"We understand our re-imposition of sanctions and the coming pressure campaign on the Iranian regime will pose financial and economic difficulties for a number of our friends. But you should know that we will hold those doing prohibited business in Iran to account," he continued.
Pompeo criticized the nuclear deal for its "fatal flaws," and the Obama administration for pursuing it.
He also called Iran an international menace that must end all support of terrorists such as Hezbollah, Hamas, and the Islamic jihad.
The secretary said the United States will also ask Europe to re-impose economic sanctions, in a bid to bring Iran back to the negotiating table.
He also asked for the support of U.S. allies beyond Europe, such as Australia, Japan, Jordan, and Saudi Arabia.
If they don't join the U.S., some see that as a costly choice.
"If they continue taking their rhetoric to the most logical conclusion that means they would be willing to side with the worlds foremost state sponsor of terrorism as opposed the state's best economy," said Behnam Ben Talebu with the Foundation For Defense of Democracies.
Dr. Nile Gardiner, with the Heritage Foundation, said, "America's enemies must understand that the United States will stand up to those who threaten the free world."
Reaction came swift from Israeli's Prime Minister Benjamin Netanyahu.
He said anyone who wants to "stop Iranian aggression and support peace, should support the United States, just like Israel does."
While a spokesman for the Iranian Foreign Ministry called the new policy "ridiculous and embarrassing and more like a satire."
Secretary Pompeo says the U.S. demands are not unreasonable and welcomes Iran's leaders to take a different path.
He adds it's ultimately up to the Iranian people to decide their future.
"We will continue to work with our allies to counter the regime's destabilizing activities in the region, block their financing of terror, and address Iran's proliferation of missiles and other advanced weapons that threaten peace and stability," Pompeo said in the speech. "We will also ensure Iran has no possible path to a nuclear weapon -- ever."
Watch Secretary Pompeo's address below.