The 23-year-old star was the centre of a viral "deepfake" video reimagining the 1985 time-travel comedy, which used digital technology to map Holland's face onto Michael J. Fox's Marty McFly, and Robert Downey Jr.'s face onto Christopher Lloyd's Doc Brown.
While the clip sparked a resurged interest in a revival, the "Spider-Man: Homecoming" actor insisted he's not on board with the idea.
"I would not be interested because that is a perfect movie," he told Entertainment Tonight.
He went on to explain that playing the character would also be redundant when it came to his own body of work.
"When I first got Spider-Man, my goal was to be my generation's Marty McFly," Holland explained. "When I was on the press tour, a journalist said to me, 'You realise you're like Marty McFly in this movie?' And I was like, '(OK!) Done.' "
Director Robert Zemeckis has previously branded talk of a remake "outrageous," telling Britain's The Daily Telegraph newspaper, "Oh, God no... That can't happen until both Bob (Gale, screenwriter) and I are dead. And then I'm sure they'll do it, unless there's a way our estates can stop it."
In accordance with the contracts the pair signed, the two men have the final say on the production of any "Back to the Future"-related films for as long as they live.
The increased interest in the franchise comes ahead of the launch of "Back to the Future: The Musical" at Manchester Opera House in the U.K. on Thursday.