Twenty-five years after the notorious killing spree led by Billy Loomis and Stu Macher in Woodsboro, tragedy strikes again when high school student Tara Carpenter faces a terrifying attack from Ghostface, leaving her hospitalized. Meanwhile, her estranged older sister Sam Carpenter learns about Tara's ordeal from her friend Wes Hicks. Determined to support her sister, Sam travels back to Woodsboro with her boyfriend, Richie Kirsch, and reunites with Tara's circle, which includes friends Amber Freeman, twins Chad and Mindy Meeks-Martin, and Liv McKenzie.
The night takes a dark turn when Liv's ex-boyfriend Vince Schneider, a nephew of Stu, falls victim to Ghostface. During a harrowing encounter at the hospital, Sam confides in Tara about her struggles with hallucinations of Billy, whom she discovers is her biological father—a truth that fractured their family and led to her estrangement from Tara. Seeking assistance, Sam and Richie reach out to Dewey Riley, who is now divorced from Gale Weathers. Dewey alerts both Gale and Sidney Prescott about the resurrection of Ghostface's terror.
As they gather to strategize, Mindy proposes that the killer is crafting a "requel," revamping the story by using Tara and her friends as the contemporary cast and weaving in Sam's connection to Billy. This theory proves dangerous when Ghostface strikes again, brutally murdering Wes and his mother, Sheriff Judy Hicks. In a twist of fate, Tara and Richie find themselves in danger but are unexpectedly rescued by Dewey and Sam. Tragically, Dewey sacrifices himself while attempting to confront Ghostface.
Following Dewey's death, Sidney arrives and implores Sam to aid in capturing the killer. However, Sam feels compelled to leave with Tara and Richie. As they head to Amber's house, the site of the original Woodsboro massacre, they join a party in memory of Wes. It is here, amidst celebration, that chaos erupts: Amber reveals herself as a killer by executing Liv with Dewey's gun, throwing everyone into a whirlpool of horror.
In shocking revelations, Richie displays his true colors as Amber's accomplice during a showdown in the kitchen, the very battleground where Sidney once faced off against Billy and Stu. The couple expresses their dissatisfaction with the latest Stab film, claiming they aim to revitalize the narrative with their own murderous spree and frame Sam as the villain. In a desperate bid for survival, Sam fights back against Richie while Sidney and Gale confront Amber.
The tension peaks when Amber, struggling and burned, attempts to resume her attack but is fatally shot by Tara. Sam gains the upper hand, finally striking down Richie with the very knife that allowed Amber to cause chaos.
As ambulances arrive to whisk Tara and the surviving Meeks twins to the hospital, a moment of gratitude is exchanged between Sam, Sidney, and Gale. Gale commits to honoring Dewey's legacy by forgoing a book on the murders. As the events of the night are captured in the news, Sam joins Tara in the ambulance, reflecting the turmoil they've endured together.
