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.

A New York cop and his wife go on a European vacation to reinvigorate the spark in their marriage, but end up getting framed and on the run for the death of an elderly billionaire.

Teenage explorer Dora leads her friends on an adventure to save her parents and solve the mystery behind a lost city of gold.

Lifelong friends Barb and Star embark on the adventure of a lifetime when they decide to leave their small Midwestern town for the first time - ever.