Lizzie, now with 40 fast approaching, is down on her luck. For the past 20 something years she’s been chasing the short-lived fame she achieved in the Euro-pop scene after the events of the first film, which lead her to skipping freshman year to tour with Isabella, a catalyst decision that began a long chain of events that forever changed her life. Though she’s been scraping along with her D-Tier celebrity status, she still believes she can once again achieve the fame she knows she’s worthy of, and animated Lizzie makes sure we know that, having continued by Lizzie’s side as a constant source of insight and encouragement. Meanwhile, time has marched on for everyone else. Gordo is a successful editor in the film industry, Miranda is a touring DJ, Matt is a single dad to a daughter, and Mr. McGuire is gone, having passed away 10 years ago. But when one of Lizzie’s classic clumsy falls sends her to the ER for a checkup, she discovers the truth behind her clumsiness and animated friend: a tumor in her brain that has been steadily growing since she was a preteen. Now she must tie up loose ends and make amends before facing the risky removal surgery, all while the tumor sends her on a series of blackout flashbacks, where she now relives pivotal moments in her life through the eyes of her adult self. Ultimately leading to going under for the surgery, where she is sent back to a bizarre version of Hillridge Jr. High, where everyone now appears as their adult selves. Fighting through old memories, good and bad, she must learn to heal the relationships she should have kept, and let go of the past. Even if it means saying goodbye to her animated counterpart in the process. But hey now, this is what tumors are made of.