Starring Ben Stiller as a museum night security guard named Larry Daley, the first 3 films also star an ensemble cast featuring Robin Williams, Owen Wilson, Ricky Gervais, Steve Coogan, Patrick Gallagher, Rami Malek, Mizuo Peck, Mickey Rooney, Bill Cobbs, Brad Garrett and Dick Van Dyke, while the video game and 4th film feature a recast ensemble of voice actors.

However, a seemingly easy job turns out to be a wild ride when he finds that an ancient spell has caused the exhibits of the museum to come to life.

Larry must break in and team up with his old friends, and new ally Amelia Earhart, to get it back from Ahkmenrah's resurrected evil older brother Kahmunrah before morning.

He and his now-teenage son Nick, along with Teddy Roosevelt, Sacagawea, Jedediah, Octavius, Dexter, Attila the Hun, and a new caveman figure named Laaa (who looks like Larry) travel to the British Museum in London to undo the curse, with the help of Ahkmenrah's parents and the narcissistic Sir Lancelot of Camelot, before the tablet's magic disappears forever.

In September 2022, Matt Danner revealed he was directing the film; he previously was the creator and showrunner of the Disney animated show Legend of the Three Caballeros (2018).