Cotton Weary (Liev Schreiber), now living in Los Angeles and the host of a nationally syndicated television show, 100% Cotton, is called by Ghostface, who demands the whereabouts of Sidney Prescott (Neve Campbell), who has gone into seclusion since the events at Windsor college. Cotton refuses to answer even when the caller claims to be in Cotton's house and threatens to kill his girlfriend. Cotton tries calling home, but his girlfriend does not pick up, as the phone line had been cut. Cotton tries calling 911, but the wait time is too long. Meanwhile the killer uses a voice changing device to mimic Cotton to lure his girlfriend Christine out and attacks her. Christine manages to lock herself into a room with the killer taunting her in Cotton's voice.
Cotton reaches home, and Christine attacks Cotton believing that he is the killer who had attacked her. Both Cotton and Christine (Kelly Rutherford) are murdered.Detective Mark Kincaid (Patrick Dempsey) meets with Gale Weathers (Courteney Cox Arquette) to discuss the murders. Kincaid reveals that the murderer left a photo at the crime scene, which Gale identifies as that of Maureen, Sidney's mother.
This prompts Gale to travel to Hollywood, where she finds Dewey Riley (David Arquette) working as an advisor on the set of Stab 3, the third film in the film within a film series based on the Ghostface murders. Cotton had recently recorded a cameo for the movie and was well known on the sets.
Ghostface kills Stab 3 actress Sarah Darling (Jenny McCarthy) (who was playing the role of Casey from Woodsboro) with the help of a voice changer (imitating the movie's director Roman), halting the film's production to the frustration of director Roman Bridger.Sidney is now living in an isolated home as a crisis counselor for an abused women's hot-line, as she is terrified that another killer may strike. Her property is protected with several layers of security devices. Sidney learns from the news that Cotton has been murdered. Sidney starts having nightmares about Maureen haunting her and Ghostface attacking her.
Having discovered her number, the killer begins taunting Sidney using a voice changer to sound like her deceased mother Maureen Prescott (Lynn McRee). Sidney travels to Hollywood, realizing she is no longer safe.As the remaining Stab 3 cast gather at the home of Jennifer Jolie (Parker Posey) who is playing the role of Gale weathers in the movie. Ghostface kills her bodyguard Steven Stone (Patrick Warburton) and uses a gas leak to cause an explosion, killing fellow actor Tom Prinze (Matt Keeslar). Dewey is the technical assistant for the movie production & Jennifer was attracted to Dewey, causing much irritation to Gale.Martha Meeks (Heather Matarazzo), the sister of Sidney's murdered friend Randy (Jamie Kennedy), visits Sidney and the others to deliver a videotape that Randy made before his death. Randy posthumously warns them the rules of a horror film do not apply in the third film of a trilogy and that any of them could die. Sidney wanders on to the sets of Stab 3, which are modeled on her original house at Woodsboro & is attacked by Ghostface & barely escapes.Gale and Jennifer do some digging in the Hollywood archives & figure that Maureen Prescott was an actress in Hollywood before she returned to Woodsboro and met Sidney's father. Maureen briefly worked as an actress in the 1960s under the stage name "Rina Reynolds" and had been sexually assaulted at a party held by Stab 3 producer John Milton (Lance Henriksen), who had earlier made 3 movies with Maureen.Dewey, Gale, Jennifer, and the remaining Stab 3 actors, Angelina Tyler (Emily Mortimer) and Tyson Fox (Deon Richmond), attend a birthday party for Stab 3's director Roman Bridger (Scott Foley) where Ghostface strikes.Gale discovers Roman's body with a knife in his chest in a movie-set coffin in the basement, while Angelina, Tyson, and Jennifer are killed by Ghostface at various places throughout the house. Ghostface then orders Sidney to the mansion to save Gale and Dewey's lives, as they are tied up. When she arrives, Ghostface forces Sidney to remove her firearm but she reveals a hidden one, which she uses to shoot the killer. As Sidney is untying Gale and Dewy, Ghostface's body disappears. Detective Kincaid shows up but is knocked out by Ghostface.Sidney flees and hides in a secret screening room where she encounters Ghostface. He reveals himself as Roman, having faked his death and survived being shot due to a bulletproof vest. Roman explains that he is Sidney's half-brother and the product of Maureen's sexual assault. Four years prior, he tracked Maureen down, only for her to reject him.Bitter over the rejection, he would film all the men she philandered with. He showed Billy Loomis the footage of his father with Maureen, which motivated him to kill her (sparking the events at Woodsboro and Windsor). However, when he discovered how much fame Sidney got because of those events, Roman snapped and lured Sidney out of hiding.
After Roman reveals a bound Milton and slits his throat, Sidney furiously denounces his explanation as nothing more than deflection to hide his selfish motivations. Roman suffers a mental breakdown and attacks.Sidney and Roman have a ferocious fight, and he ends up shooting her. While preparing for Gale and Dewey to arrive, Roman is now surprised to see that Sidney's body has disappeared. As he begins to place a call to Sidney's cellphone to locate her, he instead receives an incoming call from her. This distracts him long enough for Sidney to stab Roman in the back, apparently killing him, but not before showing him that she too was wearing a bulletproof vest. Dewey and Gale arrive, and Roman suddenly jumps up and attacks again, only for Dewey to kill him with a shot to the head.In the aftermath of the murders, Dewey proposes to Gale, which she accepts as Sidney arrives. Sidney is invited to join Dewey, Gale, and Detective Kincaid to watch a movie. As she goes to join the others, a door behind her opens, but she walks away leaving it as is, finally confident that the murders have ended and that she is now safe.
Storyline
A new film is currently in production, and a killer is on the loose. The murders draw a reporter, ex-cop, and young woman to the set of the movie inspired by their life. They soon find out that they are dealing with a trilogy, and in a trilogy...anything can happen. — mike Sidney is hibernating in the woods, her whereabouts are unknown to everyone but Dewey. After a number of murders that seem to be related to the Woodsboro case take place on the set of Stab 3, Sid comes to Hollywood to be terrorized, find out more about her mother's death, and put together the final pieces of the Scream mystery. — In the final installment to this trilogy, a murdering spree begins to happen again; this time targeted toward the orginal Woodsboro survivors and those associated with the movie-inside a-movie, Stab 3. Sydney must face the demons of her past to stop the killer(s). — reese7 While "Stab 3" is in production, somebody in a ghost mask starts to murder the new cast members. This lures Sidney out from hiding deep in the woods where she lives, and she comes to Hollywood to face the killer for the final act. — T-2