Larry Daley has left his night guard position at the museum and is now CEO of his own, successful, company which sells his inventions on shopping channels - such as the 'glow in the dark flash light'. On a rare visit to see his old friends at the museum, he learns that most exhibits are to be shipped to the larger vaults of the Smithsonian, without the life-giving Egyptian tablet. However, one night he receives a call from Jedediah begging for help - it seems the tablet was taken with them to the new museum, and his friends are under attack!

Larry and Amelia use the bobblehead Einsteins to solve the riddle of the tablet - the sequence that must be entered is the first 8 numbers of PI. To save Jedediah's life, as he is trapped in an hour glass, Larry tries to negotiate with Kahmunrah - until the gangsters turn up, with the bobbleheads, and tell the Pharoah the correct sequence.
  The black tomb opens and out march an army of bird men. They surround Larry. Suddenly the giant Abe Lincoln crashes through the huge window and scares the bird men - who run back into the tomb. His final advice to Larry is to divide the enemy before he leaves.
  Amelia shows up with their old friends - and there's a huge battle between the good guys and those on the dark side. General Custer is scared, but Larry wins him over and together they lead the good guys to victory.
  Larry is cornered by Napolean, Al Capone and Ivan - but he successfully manages to get them fighting together by telling them he'll give the tablet to the leader.

Larry and Kahmunrah duel - with a scythe against Larry's flashlight. Larry is victorious and the Pharoah is knocked back through the tomb and into the underworld.
  Realising it is starting to get light again, the giant squid is taken outside for a quick dip in the pool and the New York mannequins are flown back to the Big Apple by Amelia.
  The heroes from the first movie exit the tiny plane Mary Poppins style, and are welcomed back. Amelia kisses Larry and then flies off into the distance and sunrise.

A little in the future, Larry is back working as a night guard at the Natural History museum - and we learn from Ricky Gervais's character that an anonymous donor left a small fortune to the museum on condition that it opens after dark. All the heroes are working - storytelling and leading guided tours, while the visitors assume most things are working through animatronics.
  A young lady enters who looks just like Amelia (probably because the actress is Amy Adams) and catches Larry's eye. They flirt, and she asks him for a guided tour.

In the credits we go back to the guy in the b/w victory poster trying to figure out Larry's phone - and we find out his surname is Motorola.