On the 15th anniversary of the tragic Woodsboro murders, a fresh wave of terror erupts when high school students Jenny Randall and Marnie Cooper fall victim to the notorious Ghostface. On the very next day, Sidney Prescott returns to her hometown, accompanied by her publicist, Rebecca Walters, to promote her self-help book, only to find herself entangled in a new mystery. After incriminating evidence is discovered in her rental car, Sidney becomes the prime suspect in these gruesome murders and must remain in Woodsboro until the case is resolved.
Amidst the chaos, Sidney's cousin, Jill Roberts, is grappling with the fallout from her ex-boyfriend, Trevor Sheldon, and receives a threatening call from Ghostface that sends chills down her spine. Her friend, Olivia Morris, is also caught in the killer’s web of fear. As they are questioned by Dewey Riley, now Woodsboro’s sheriff, his deputies, Judy Hicks, Anthony Perkins, and Ross Hoss, lend their support in unraveling this sinister plot. Meanwhile, Gale Weathers, Dewey's wife, is battling her own writer's block, which leads to her determination to investigate the murders, much to her husband’s dismay.
That fateful night, while staying with Jill and her aunt, Kate, tragedy strikes when Ghostface brutally kills Olivia, leaving Jill and her friend Kirby Reed powerless from across the street. Sidney confronts Ghostface shortly after, leading to a chaotic struggle that ends with Ghostface's hasty retreat as the cops arrive. Over at the hospital, Sidney dismisses Rebecca after realizing she intends to exploit the murders for personal gain. The horror escalates when Ghostface murders Rebecca in a parking garage.
In a desperate bid for answers, Gale teams up with two high school horror enthusiasts, Charlie Walker and Robbie Mercer. Charlie theorizes that the killer is mimicking the tropes of horror remakes, leading them to believe the next attack will occur at the “Stabathon” screening party—an event where teens gather to watch all seven films from the Stab franchise. Gale infiltrates the party to gather information but becomes a target herself when Ghostface stabs her in the shoulder. As the body count rises and Hoss and Perkins are also slain, Sidney uncovers the alarming truth: Jill has left for Kirby's place just before another attack ensues, leading to the tragic death of Kate.
The horror escalates further as Jill, Kirby, Charlie, Robbie, and Trevor gather for an after-party at Kirby's home, where Ghostface once again strikes, taking down Robbie in a shocking twist. Just when Sidney and Jill plan to leave, they find themselves on the run from Ghostface. In a dramatic turn of events, Charlie, revealed as Ghostface, brutally stabs Kirby. But the most shocking reveal comes when Jill unveils her twisted plan, motivated by jealousy of Sidney's fame and aiming to spin herself into a pseudo-victim role. Her ruthless ambition leads her to eliminate Trevor and Charlie, attempting to frame Trevor as Ghostface's accomplice so she can emerge as the sole survivor amidst the carnage.
As the grisly showdown unfolds, Dewey and the police rush to the hospital where Sidney and Jill find themselves. However, things take a dangerous turn when Jill, enraged to discover Sidney has survived, makes a final, desperate attempt to finish what she started. But Sidney proves to be more resilient than ever. In a tense confrontation with Dewey, Gale, and Judy aiding her, the truth out about Jill’s role as the killer is revealed. A fierce confrontation ensues, ending in Sidney’s triumphant defiance as she ultimately incapacitates Jill with a defibrillator and delivers a fatal shot to her heart. With the chaos settled, Dewey promptly calls in all police units, while outside, reporters mistakenly dub Jill the "sole surviving hero," a title she does not deserve.
