The nod raises questions about potential conflicts of interest, given Isaacman's financial ties to SpaceX chief Elon Musk, who is set to co-lead a government efficiency commission and is one of Trump's closest advisors.
Isaacman, the 41-year-old founder and CEO of Shift4 Payments, has emerged as a leading figure in commercial spaceflight through his high-profile collaborations with SpaceX.
He made history in September by stepping out of a Crew Dragon to gaze at Earth from the void of space while gripping the spacecraft's exterior, during the first-ever spacewalk carried out by non-professional astronauts.
"I am delighted to nominate Jared Isaacman, an accomplished business leader, philanthropist, pilot and astronaut, as Administrator of the National Aeronautics and Space Administration (NASA)," Trump wrote on Truth Social.
"Jared will drive NASA's mission of discovery and inspiration, paving the way for groundbreaking achievements in Space science, technology, and exploration."
- SpaceX ties -
The groundbreaking spacewalk was part of the Polaris program, a collaboration between Isaacman and SpaceX that is set to include three missions in total, culminating in the first crewed test of the next-generation Starship.
Financial terms of the initiative remain under wraps, though the matter is likely to come up during Isaacman's Senate hearings.
Isaacman reportedly poured $200 million of his own money into leading the 2021 all-civilian SpaceX Inspiration4 orbital mission, his first foray into space.
A staunch supporter of SpaceX and Musk, Isaacman frequently praises the company and its vision on social media platform X.
"There will inevitably be a thriving space economy -- one that will create opportunities for countless people to live and work in space," Isaacman said in an X post after Trump's announcement. "At NASA, we will passionately pursue these possibilities."
Isaacman, a Pennsylvania native, founded the business that became Shift4 Payments from his family's basement at just 16.
A skilled aviator, he is qualified to fly military aircraft, has performed at airshows, and set a world record for an around-the-world flight.
- Future direction of NASA -
The nomination comes at a delicate juncture for the storied US space agency, with experts anticipating significant shifts in direction during Trump's second term.
The Artemis program, which aims to return astronauts to the Moon, may face scrutiny as Trump has repeatedly voiced a preference for prioritizing a direct mission to Mars.
Also possibly on the chopping block is the massive, NASA-owned Space Launch System (SLS) Moon rocket, which has been criticized for being exorbitantly expensive due to its lack of reusability, in contrast with SpaceX's Starship, which is designed to be reusable but remains a prototype.
If Isaacman is confirmed by the Senate, his ties to SpaceX could invite heightened scrutiny of future contracting decisions.
NASA currently has agreements with both SpaceX and Jeff Bezos's Blue Origin to develop lunar lander systems -- an approach Isaacman has criticized, citing budgetary constraints and SpaceX's capabilities.
"Congress is going to have to do its job here and exercise oversight," Peter Juul of the Progressive Policy Institute told AFP, urging lawmakers to mandate dual-source contracting so NASA "doesn't become a glorified contracting agency for SpaceX."
Still, as a swashbuckling entrepreneur in an era of expanding public-private partnerships in space, Isaacman's appointment has drawn praise in some quarters.
"The Planetary Society shares his vision of bold exploration in space, and, should he be confirmed, we look forward to working with him," Casey Dreier, the nonprofit's chief of space policy, told AFP.
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