The story starts off on a clichéd note, but gains ground after a while. We have Ben Stiller who plays the character Larry. Yet again, he plays a clumsy, unsuccessful (and unintentionally funny) divorced man who is struggling to find a stable job. Despite loving his 10-year old son Nick to death (the role of the child is played by child artist Jake Cherry of the ‘Miracle Run’ Fame), he is unable to give him a stable, well-provided life or establish himself as a good role model. Larry’s ex-wife Erica (played by Kim Raver in a small role) is not able to fathom what to do with her bumbling ex-husband who always finds himself at the wrong places at the wrong time, and is not able to set a positive example for their impressionable son.
So when he stumbles across the job opportunity of a night watchman at the Museum of Natural History, he jumps at the prospect. Despite being given a manual about his duties as a night watchman, Larry discovers the secret behind why the museum is losing so much money, and why it is about to be shut down in some time. The fact is that most of the museum exhibits frighteningly (and somewhat comically) come alive at night. This includes a tyrannosaurus Rexy that barks like a dog, Dexter the monkey that mischievously tears up poor Larry’s ‘watchman manual’ etc. One can also find more commonly known, yet amusing characters like Attila the Hun, the Easter Island Moai, Octavius the Roman General and Theodore Roosevelt.
While Roosevelt temporarily controls things for one night, it is up to Larry to keep things under control every other night. The crux of the matter is that ever since an Egyptian Artifact was included amongst the museum’s exhibits, the lifeless exhibits have automatically started coming to life owing to its supernatural powers. But of course, this happens only at night, and if any of the so-called ‘live exhibits’ are exposed to sunlight, they will automatically turn to dust and disappear. Now in the absence of the instruction manual that was torn up by the monkey, Larry must study history and prepare himself for the impending challenges. Unfortunately, he is in for a shock when a Neanderthal exhibit that came alive, set fire to the museum. Also, one of the escaping Neanderthals is exposed to sunlight and disappears into thin air. When the Museum Director comes to know of the ‘mysterious disappearance’ of the precious exhibit, he gets furious and almost fires Larry for his carelessness.
In the nights to come, there is further ruckus, till Larry finally convinces the museum management to see the fact that exhibits are actually coming alive. This happens when the museum docent Rebecca sees this happen in the wee hours of the morning, as well as sees mysterious footprints and cave paintings in the sub-way station of the museum. Despite all the chaos and confusion, in the end of it all, the museum benefits as there are a lot of news reports and press coverage. So with all the newfound attention, the number of visitors and ticket sales spike up, and the almost-bankrupt status is redeemed. Larry is hailed as the savior and his temporary firing from his position, is nullified.