Larry Daley and his heroic friends embark on the greatest adventure of their lives, as they travel to London to save the magic that, after dark, allows the museum's exhibits to come to life.

A well-intentioned, but bumbling security guard at the Museum of Natural History is taken on the adventure of a lifetime when an ancient curse brings to life all of the artifacts in the museum and threaten to wreak havoc in the city.

Fifteen years after his appearance in the BBC2 "documentary" series ''The Office'', David Brent is a sales rep for bathroom supply firm Lavichem. His colleagues include his nemesis, Jezza, who cannot stand Brent or his jokes; however, he gets a more sympathetic response from colleague Pauline and receptionist Karen, and shares the same sense of humour as fellow sales rep Nigel.

Two years after the events of the first film, Larry Daley, former night guard at the American Museum of Natural History, now runs his own direct response television company that sells inventions based on his experiences. He travels to the museum, discovering most of the exhibits will be moved to the Federal Archives at the Smithsonian Institution and replaced with holographic information providers. The Tablet of Ahkmenrah is to remain in the museum, leaving most of the exhibits without the ability to come to life at night. After the exhibits are moved, Larry receives a phone call from Jedediah, who informs him that Dexter the monkey stole the tablet and took it to the Smithsonian, bringing every exhibit in it to life. Larry travels to Washington, DC, navigating his way to the archives with help from his son Nick while posing as a night guard.