Set several decades after the events of the original film, the sequel follows the unlikely return of Madeline Ashton and Helen Sharp, who continue their eternally youthful rivalry while attempting to navigate a world that has changed dramatically around them. Having spent years hiding from the public eye to avoid suspicion about their ageless appearances, they now discover that their immortality has become more burden than blessing. When a powerful billionaire announces a technological breakthrough promising eternal youth, rumors begin spreading that he possesses a formula similar to the mysterious potion they once took. Fearing exposure and desperate to protect their secret, Madeline and Helen reluctantly reunite to investigate the situation.

Their search leads them to a wellness empire in California, where the billionaire, Adrian Vale, claims to offer “ageless transformation” through a process that seems disturbingly familiar. Madeline suspects he has recreated the potion, while Helen believes he may have stolen the original recipe from the secret society they once encountered. Their constant bickering and competitive impulses complicate their efforts, but their shared fear of becoming obsolete forces them to cooperate. As they infiltrate Vale’s inner circle, they discover that his treatments have dangerous side effects, causing rapid decay in those who receive incomplete doses.

Madeline and Helen disguise themselves as wealthy clients to gain access to the restricted areas of the facility. Their immortality, however, creates complications: their bodies still carry the cracks, dents, and imperfections from decades of mishaps. They must constantly repair themselves, leading to darkly comic situations where they struggle to appear flawless in front of Vale’s staff. Their physical challenges highlight the consequences of eternal life, underscoring the difference between preserving beauty and preserving the self.

As they uncover more about the operation, they learn that Vale intends to mass-produce a diluted version of immortality, potentially subjecting the world to catastrophic results. His ambition threatens not only humanity but also their own existence, since exposure of immortality would turn them into test subjects or global curiosities. Despite their usual self-centered tendencies, they realize they must stop him before society descends into chaos and their secret becomes impossible to hide.

The climax brings Madeline and Helen face-to-face with Vale in an elaborate confrontation inside his laboratory. Their immortality, though flawed, gives them a brief advantage, allowing them to sabotage the production line and destroy the unstable formula. The destruction triggers a series of crises within the facility, forcing them to escape while their bodies continue to fall apart in slapstick fashion.

In the aftermath, the two women find themselves once again on the run, but with a new understanding of their strange bond. While they still argue and undermine each other, they accept that their immortality has intertwined their fates irrevocably. The film ends with them heading into an uncertain future, cracked but unbroken, united by the shared absurdity of living forever.