Nathan Jung loves visiting the American Museum of Natural History as much a boy his age enjoys video games. But after finding himself locked in one night with night guard and family friend Larry Daley well...he just might realize things truly are more 'alive' after all when the sun sets.

Nathan thought things would finally be calm after the defeat of Kahmunrah. That he and Ahkmenrah could start a somewhat 'normal' relationship with each other. He should have known better than that. When Ahkmenrah's tablet goes awry and loses the power it holds, Nathan, Larry and Nicky fear this may be the end for their friends.

Nathan's held horrible feelings of late, that come to be as truth. All the museum exhibits except Ahkmenrah and his Tablet, will be shifted off towards the Smithsonian forced to be inanimate. But all may not be a total loss, as new allies are made (Did they really find, Amelia Earhart?), new foes and hidden emotions revealed.