On October 29, 1998, Michael Myers (Chris Durand), burglarizes Dr. Sam Loomis' (voiced by Tom Kane) retirement house in Langdon, Illinois. Loomis' former colleague, Marion Chambers (Nancy Stephens), who took care of Dr. Loomis until he died, arrives and discovers that the file on Laurie Strode (Jamie Lee Curtis), who is presumed dead in an automobile accident, is missing. Michael murders her, her teenage neighbor Jimmy (Joseph Gordon-Levitt) and his friend Tony (Branden Williams), before leaving the house with Laurie's file.
In Summer Glen, California, Laurie, having faked her death to avoid Michael, lives under an assumed name "Keri Tate", having a career as the headmistress of Hillcrest Academy, a private boarding school. Laurie is also in a relationship with Hillcrest guidance counselor Will Brennan (Adam Arkin). However, Laurie is far from happy, as the tragic events from 1978 still haunt her; she lives in fear that her brother may return for her. While a woman and her daughter are at a rest stop, Michael steals their car. At the academy campus, the students leave to attend a school trip to Yosemite, leaving only Laurie, Will, security guard Ronny Jones (LL Cool J), Laurie's son, John, (Josh Hartnett) and his girlfriend Molly Cartwell (Michelle Williams) and their classmates Charlie Deveraux (Adam Hann-Byrd) and his girlfriend Sarah Wainthrope (Jodi Lyn O'Keefe), who are having a Halloween party in the school basement.
Later that night, Laurie reveals her true identity to Will and realizing that Michael has most likely returned to kill her upon realizing that John is the same age she was when the murders from 1978 happened. Michael, meanwhile arrives with a stolen old panel truck at Hillcrest and kills Charlie and Sarah. John and Molly are chased by Michael through the school grounds. Will and Laurie save John and Molly from Michael, and he and Laurie come face-to-face for the first time in twenty years. Will accidentally shoots Ronny, who had been patrolling the hallway, when he mistakes Ronny's shadow for Michael, and Michael kills Will while Will and Laurie are examining Ronny's body.
Laurie manages to get John and Molly to safety, and realizing that she'll never be safe from Michael as long as he's alive, starts fighting Michael face to face. Laurie stabs Michael numerous times and pushes him over a balcony. She prepares to stab him again, but Ronny, who survived the shooting, convinces her to stop. The authorities arrive at the scene and load Michael into a coroner's van, but Laurie, knowing that Michael is still alive, steals the van to kill him for good. Michael awakens and attacks Laurie, who stops, causing Michael to fly through the windshield. Laurie drives the van into Michael, and she proceeds to drive off the road, down a steep hill. Laurie tumbles out, and Michael is pinned between the van and a tree. Michael reaches out to Laurie and they almost touch hands right before she decapitates him with a fire axe.
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