Spencer Gilpin, feeling disconnected from his college life and longing for the confidence he possessed as his avatar Dr. Smolder Bravestone in the video game world of Jumanji, secretly keeps the game's pieces. Against his friends' agreement to destroy the dangerous game, he repairs it in a bid to return to his heroic persona. When Spencer mysteriously vanishes, Martha, Fridge, and Bethany, his friends from the previous adventure, discover the game running in Spencer's basement and realize he is inside. Deciding to rescue him, they jump back into Jumanji's perilous jungle, but things don't go as planned. This time, the game malfunctions, pulling in additional unwitting players: Spencer's grandfather, Eddie, and Eddie's estranged friend, Milo. Moreover, the group discovers that they are in new avatars with different skills and weaknesses, complicating their mission.

As the team ventures through the unpredictable game, they face new challenges and environments, including arid deserts and snowy mountains far beyond the jungle they previously conquered. They must quickly adapt to their swapped avatars, capitalize on their unique abilities, and hunt for Spencer. All the while, they grapple not only with the game's increasingly difficult levels but also internal strife and unresolved issues among themselves and the new elderly duo. The stakes are higher, the dangers more severe, and their teamwork and friendship are tested as they strive to escape Jumanji once more and bring everyone home safely.