Led by Senator Ted Cruz, a long-time opponent of the 2015 nuclear deal, the senators told Biden in a letter dated Monday that they would use "the full range of options and leverage available" to ensure that his government adhered to US laws governing any new accord with Iran.
Indirect talks in Vienna between Iran and the United States on reviving the 2015 agreement are due to resume on Tuesday.
Talk of a possible agreement has driven oil prices lower, with markets anticipating that the possible removal of sanctions on Iranian oil sales could boost global supplies.
The Biden administration has been trying to revive the deal, which lifted sanctions against Tehran in exchange for restrictions on its nuclear activities, a deal from which former President Donald Trump withdrew the United States in 2018.
Iran later breached many of the deal's nuclear restrictions and kept pushing well beyond them.
Cruz and other senior Republican senators told Biden that implementation of any new deal would be "severely, if not terminally hampered" if he did not meet statutory obligations aimed at ensuring congressional oversight over revisions or changes to the 2015 Iran nuclear accord.
They provided no details about their plans, but Republicans have used various tactics to slow down other legislation or put holds on Biden's nominees, including many for ambassador posts.
Democrats control the 50-50 Senate only by virtue of a tie-breaking vote that can be cast by Vice President Kamala Harris, but they could lose control of the Senate and the House of Representatives in mid-term elections later this year.
The senators said any nuclear agreement with Iran was of "such grativity for US national security" that it would by definition be a treaty requiring the advice and consent of two-thirds of the Senate, they argued.
Any deal that fell short of Senate-ratified treaty would "likely be torn up in the early days of the next presidential administration," they added, anticipating a Republican victory in the 2024 presidential race.
In addition, they noted that a 2015 law passed before completion of the initial nuclear deal requires that any new "agreement" related to Iran's nuclear program to be transmitted to Congress for a 60-day review period during which Congress could pass a joint resolution of disapproval that would essentially prevent the deal from going into effect.
It said those mandates would be triggered by Iran's progress toward developing a nuclear weapon over the past year, which would require new oversight measures.
