Following a painful divorce, financially unstable father Larry Daley takes a job as a night security guard at the Museum of Natural History. However, as he meets his cryptic three predecessors, he is in for a big surprise as strange things start to happen from day one. Now animated by an unfathomable mystical force, the entire museum comes to life at sunset, and no one can stop the vigorous exhibits from wreaking havoc. But who, or better yet, what is behind the uncanny incident? Can Larry survive his first night at the museum?