During a White House speech at 12:45 pm (1645 GMT), Trump is expected to declare a 2015 deal, which curbed Iran's nuclear program in return for massive sanctions relief, is no longer in the US national interest.
Officials say he will not kill the deal outright, or designate Iran's powerful Islamic Revolutionary Guard Corps a terrorist organization -- a move that would almost certainly bring retaliatory action.
Instead he will leave US lawmakers to decide whether they want to kick away one of the accords foundational pillars by "snapping back" sanctions against Iran.
Many lawmakers are waiting to see how Trump presents the choice, with no clear consensus even among Republicans on whether to torpedo the agreement.
In a statement to AFP, leading Republican Senator Marco Rubio described the accord as "fatally-flawed" and said he was open to legislation that would "substantially improve America's ability to counter Iran's nuclear, terrorism, militancy and regional threats."
While Trump's decision is largely rhetorical -- designed to meet a key campaign pledge -- it risks unpicking years of careful diplomacy and increasing Middle East tensions.
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.
Secretary of State Rex Tillerson spent much of the week on the telephone, talking through a decision that is deeply unpopular with allies.
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.
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."
Iranian President Hassan Rouhani lashed out at US counterpart saying he was opposing "the whole world" by trying to abandon a landmark nuclear agreement.
"It will be absolutely clear which is the lawless government. It will be clear which country is respected by the nations of the world and global public opinion," he added.
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.