Three years after leaving his career as a stripper, Mike, portrayed by Channing Tatum, has started anew by running his own furniture business. His tranquil life is disrupted when he receives an unexpected call from Tarzan, played by Kevin Nash, conveying the shocking news that Dallas is "gone." Initially believing that his former boss has died, Mike rushes to a hotel only to realize that his friends, the remaining Kings of Tampa, are having a blast at a pool party. The revelation hits him hard: Dallas has left to start a new show in Macau, taking "The Kid" along with him. The Kings propose an exhilarating plan to conclude their careers on a high note by attending a stripping convention in Myrtle Beach.
Inspired by a nostalgic song from his past, Mike rekindles his passion and decides to embark on this adventure with his friends. They set off in a fro-yo van owned by Tito and Tobias, portrayed by Adam Rodríguez and Gabriel Iglesias respectively. Their first stop is Mad Mary's, where Mike enters an amateur queen contest to prove his commitment to the trip, and soon the others join in, spurring a series of unforgettable moments.
As they make their way to the beach, Mike attempts to mend his relationship with Ken, played by Matt Bomer, leading to a heartfelt reconciliation. Along the journey, Mike meets a captivating photographer named Zoe, played by Amber Heard, who shares her plans of moving to New York. Despite their chemistry, Mike opts not to pursue anything further. The camaraderie deepens as Mike suggests they shake up their routine, leading to an amusing scene at a gas station where he maneuvers Richie, played by Joe Manganiello, into providing a spontaneous striptease to lighten the mood.
However, the road trip is not without its complications; an inebriated Tobias crashes the van, causing a rift but leaving everyone else unharmed. At the hospital, Mike candidly shares that his furniture business isn't thriving, and he also reveals that he has parted ways with Brooke. In search of a new emcee for their show, Mike and the group visit Rome's strip club, where they face rejection despite showcasing their talents. Nevertheless, Rome, skillfully portrayed by Jada Pinkett Smith, later offers them a ride to their next destination, thanks to her connection with a rapper named Andre, played by Donald Glover.
Upon arriving at a mansion, they meet Nancy, played by Andie MacDowell, who happens to be the mother of the girl expecting them. While the initial encounter is awkward, their time together turns enjoyable, and Mike once again crosses paths with Zoe. As they talk, Mike encourages her to join them at the convention to rekindle her lost smile. After a flirty encounter with Richie, Nancy permits the group to borrow her ex-husband's car to continue their journey to Myrtle Beach.
When they arrive, they are surprised to find Rome has had a change of heart and agrees to be their emcee, bringing along Andre and Malik, played by Stephen "Witch" Boss, to support their performance. Their preparations lead to an unexpected opportunity at the convention, thanks to Rome's ties with the event's organizer, Paris, portrayed by Elizabeth Banks. As their performance packs the crowd, Mike invites Zoe on stage, culminating the movie in a vibrant celebration, with Tobias returning in the fro-yo van and everyone joyously watching the 4th of July fireworks light up the sky.