In the scorching sands of the Egyptian desert in 1938, a daring group of archaeologists set out on a challenging journey to discover the tomb of the elusive Pharaoh Ahkmenrah. Among these adventurers was the youthful and determined Cecil "C.J." Fredericks (Ben Stiller), whose curiosity led him to uncover the ancient Tablet of Ahkmenrah. As the team hastily compiled their discoveries, an ominous tension swept through the air, intensified by local legends whispering through the dusty passages of the tomb: > "the end will come."
Fast forward seventy-six years to New York City, where Larry Daley (Ben Stiller) still proudly works as the night guard at the Museum of Natural History. The once quirky relic of his past has transformed into a beloved institution, and he takes immense pride in preparing for the grand reopening of the Hayden Planetarium. While making adjustments to the exhibits, Larry is surprised by a new addition: a Neanderthal mannequin named Laaa (Owen Wilson), who unnervingly claims Larry as his father.
The ancient tablet, now enshrined in the museum's storeroom for 76 years, has started to show signs of wear; its magical properties diminishing. Disarray erupts around the exhibits as the celebration for the planetarium's reopening approaches, leaving Larry exasperated, especially after returning home to find his teenage son Nick hosting a wild party.
Desperate for answers regarding the tablet’s deterioration, Larry reconnects with the now-retired archaeologist Cecil Fredericks (Ben Stiller), a key member of the original exploration team. As they unravel the ancient prophecy of "the end will come," Cecil realizes that it foretells the possibility of the exhibits losing their life unless the magic of the tablet is rekindled.
Motivated by this revelation, Larry seeks out Ahkmenrah's parents, Merenkahre and Shepseheret, whose history resides in the British Museum. Convincing the museum curator Dr. McPhee (Ricky Gervais) to allow him to transport Ahkmenrah across the Atlantic, he embarks on a quest, joined by his son Nick.
At the British Museum, they navigate through the labyrinthine corridors, attempting to evade the watchful night guard Tilly (character A). During their search for the artifacts belonging to Merenkahre and Shepseheret, they unexpectedly encounter a few spirited American exhibits who had stowed away: Theodore Roosevelt, Sacagawea, Attila the Hun, miniature figures of Jedediah and Octavius, and Dexter the capuchin monkey. The arrival of these lively characters awakens the British exhibits, igniting a thrilling escapade where Larry must protect the museum's treasures from fading into oblivion.
As they press onward, a wax figure of Sir Lancelot (actor not specified) joins their ranks and proves to be a brave ally against more threatening exhibits. Although he courageously faces down a Triceratops skeleton and Xiangliu statue, the tablet continues to deteriorate, causing unsettling transformations among the American exhibits as their bodily movements stiffen and memories blur. Eventually, they secure Ahkmenrah's parents, learning that the tablet's vitality can be restored through the magic of Khonsu, energized by the moonlight.
Unexpectedly, Lancelot confuses the tablet for the Holy Grail and sets off toward Camelot. Meanwhile, Tilly cunningly locks Larry and Laaa in the break room, but thanks to Attila's resourcefulness, they manage to break free. As they make their escape, Laaa is drawn to Tilly, igniting a romantic spark between them.
As they chase down Lancelot to an extravagant musical featuring Hugh Jackman and Alice Eve (both played by actors not specified), he realizes that his existence and that of the exhibit is merely illusory. Larry and the group catch up with him on the theater rooftop, just as the tablet risks returning everything to inanimate status.
Faced with urgency, the team must convince Lancelot that while Camelot might be fictional, he can still create a meaningful existence. With the tablet rejuvenated under the moonlight, all exhibits spring back to life. Before the American exhibits prepare to return home, they collectively decide to leave Ahkmenrah with his family at the British Museum, relinquishing their own chance for life in the process.
Though heartbroken, Larry comes to accept their choice, and Ahkmenrah expresses his gratitude for being reunited with his kin. As the exhibits embark on their new journey, Larry shares a poignant farewell before stepping out of the museum one last time.
Three years later, Larry has embraced a new role as a schoolteacher, while McPhee (played by an actor not specified) has returned to the museum. Tilly enters, ushering in a traveling exhibit in partnership with the museum. During a visit to McPhee's office, she showcases the tablet's remarkable powers, reviving the exhibits who join in jubilant celebration.
From across the street, Larry beams at the festivities, knowing that although his friends may be gone, their legacy will forever endure.
