White House spokeswoman Sarah Huckabee Sanders said Trump would unveil a broad plan to counter Iran at 12:45 pm (1645 GMT).
She did not elaborate, but Trump is expected to declare to Congress that retaining the 2015 Iran nuclear agreement is no longer in the US national interest.
This in itself does not mean the deal will collapse. US lawmakers will have 60 days to decide whether they want to "snap back" the sanctions Washington has suspended.
But it will mark a clear break with America's allies, who have pleaded with Trump to respect the accord, and a fierce blow to the multilateral international order.
The agreement was signed between Iran and six world powers -- Britain, China, France, Germany, Russia and the US -- at talks coordinated by the European Union.
UN nuclear inspectors say Iran is meeting the technical requirements of its side of the bargain, dramatically curtailing its nuclear program in exchange for sanctions relief.
Australia has urged the US to retain the nuclear deal with Iran in the absence of any credible alternatives.
"We are urging that it be maintained and Iran's other behaviour be dealt with in different circumstances," Foreign Minister Julie Bishop told ABC TV.
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So, while US officials still insist that "America First" does not mean "America Alone," on this issue they are starkly isolated. The other signatories all back the deal.
"This is the worst deal. We got nothing," Trump thundered to Fox News on Wednesday. "We did it out of weakness when actually, we have great strength."
Trump, whose address to this year's UN General Assembly was a hymn to national sovereignty, has been railing against the Iran deal since before he was elected.
Allies pleading
In office, he has chafed at being required under US law to re-certify Iran's compliance with the accord every 90 days, declaring that Tehran has broken it "in spirit."
Now, as he prepares to roll out a broader US strategy to combat Iran's expanding power in the Middle East, he feels the time has come to turn his back on the deal.
Right up until the last minute, America's closest allies have urged Trump to think again.
After his nationalist UN speech, EU foreign policy chief Federica Mogherini warned that the deal "doesn't belong to one country... it belongs to the international community."
US allies have not been convinced by the argument that the deal fell short because it left Iran free to develop ballistic missiles and sponsor proxy militias in its region.
"Mixing everything means risking everything," a French diplomatic source told AFP. "The existential threat is the bomb. The nuclear deal is not meant to solve Lebanon's problems."
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Europe fears not only that Iran will resume the quest for the bomb but that the US is relinquishing its leadership role in a stable, rules-based international system.
On Tuesday, British Prime Minister Theresa May called the White House to impress upon it her government's "strong commitment to the deal alongside our European partners."
In parallel, her foreign minister, Boris Johnson, told his US counterpart Secretary of State Rex Tillerson "that the nuclear deal was an historic achievement."
"It was the culmination of 13 years of painstaking diplomacy and has increased security, both in the region and in the UK," he argued.
But the US administration barely acknowledged the calls, and European diplomats in Washington privately complain that their message is not getting through.
'We will see'
One Western diplomat said that once Trump "decertifies" the deal their efforts will move to Congress, where they will urge US lawmakers not to re-impose sanctions.
"Our embassy is working with the legislature," German foreign ministry spokesman Rainer Breul said this week. "We are looking for dialogue, to explain our arguments."
They will find some sympathetic ears in Congress but this won't move Trump. His most senior foreign policy advisers have also urged him to back the deal, to no avail.
Last week, Secretary of Defense Jim Mattis was asked whether he believes the Iran deal remains in the US national interest.
"Yes, senator, I do," he replied.
"I believe at this point in time, absent indication to the contrary, it is something that the president should consider staying with."
Since that testimony, Mattis and Tillerson have had lunch with Trump and discussed Iran, but Trump later spoke once more against the deal on Fox television.
"We will see what happens pretty soon," Trump warned.
On Thursday, in another dramatic sign of Washington's foreign policy direction, the US announced that it was withdrawing from the United Nations science and cultural organization UNESCO.
France's UN ambassador expressed dismay, warning "we need an America that stays committed to world affairs."
