Explore a side of the Smithsonian that you've never seen before in Night at the Museum: Battle of the Smithsonian. Based on the Ben Stiller movie, gameplay takes the player from the New York Museum of Natural History to the campus of the Smithsonian. The spell of Ahkmenrah's magic tablet has brought the inanimate exhibits of the Smithsonian to life, and Larry must restore order to the chaotic museum. Players control Larry Daley (Stiller), who must retrieve the tablet of Ahkmenrah from the clutches of the evil Kahmunrah.

While basic movement mechanics (running, jumping, climbing) are used, major gameplay mechanics focus on the use of Larry's "ritual tools of office", his keychain and flashlight. These items are enhanced by the power of Ahkmenrah's tablet, which gives Larry new abilities. With the enhanced keychain, Larry can climb to greater heights, swing across wide gaps, and swing the chain quickly to create a shield. The enhanced flashlight will allow Larry to empower mechanical devices, repair broken objects, tame wild animals, and even summon lightning. Players will use these abilities to complete objectives across multiple museums.