In 1938, in Egypt, archaeologists find the tomb of the pharaoh Akmenrah, given the young Cecil Fredericks, discovering the magical tablet of Akmenrah. The Egyptians warn archaeologists that removing the tablet will end its magic. In modern New York, Larry Daly remains the night guard at the American Museum. He, Theodore Roosevelt, Sacagawea, Attila the Hun, Jedidiah, Octavius, Rexy, the skeleton of a Tyrannosaurus rex, and Dexter, a capuchin monkey, help reopen the Hayden Planetarium.
A new Larry-like wax Neanderthal named Laaa is introduced, who identifies Larry as his dad. Akmenrah reveals to Larry that the tablet is nearly corroded, which later causes the exhibits to act abnormally, causing massive havoc at the planetarium's opening. Afterwards, Larry catches his son Nick, who plans to take a year off to sort out his life by throwing a house party.
Larry reunites with Cecil, now retired, realizing that the end of the tablet's magic will cause the exhibits to become lifeless. Cecil explains that Akmenra's parents, Merenkahre and Shepseheret, may be able to restore the tablet's power, but they are in the British Museum. Larry convinces the museum's curator, Dr. McPhee, to let him send Ackmenr to London to retrieve the tablet, convinced that McPhee knows its secrets.