While his luck seems to have turned for the better, good-hearted dreamer Larry Daley (Ben Stiller) must say goodbye to his museum friends who are being replaced by virtual hologram exhibits as a stunt to make the Natural History Museum more "interactive."

As his historical pals were being shipped off to Washington, D.C., they realized that the tablet of Ahkmenrah was mistakenly taken which allowed the Smithsonian to come to life.

To save his friends, Larry must travel back to Washington D.C. to combat the Kahmunrah, Al Capone, Ivan the Terrible and French General Napoleon.