On October 29, 2018, Michael Myers, who has been institutionalized at Smith's Grove Psychiatric Hospital for 40 years following his killing spree in Haddonfield, is being prepared for transfer to a maximum-security prison. True crime podcasters Aaron Korey and Dana Haines visit the hospital and, during their encounter, Aaron displays the mask that Michael wore in 1978 to him, to no effect. The following day, as he is being transferred, Michael purposely crashes the bus, kills a father and son for their car, and returns to Haddonfield.
In Haddonfield, Laurie Strode is still living in fear of Michael; she is drinking heavily, rarely leaving her fortified house and alienating herself from her daughter Karen, whom the state took away from her at age 12. The only person she keeps in contact with is Karen's daughter, Allyson.
On the morning of October 31, Michael sees Aaron and Dana visiting his sister Judith's grave. He follows them to a gas station where he kills them both, as well as a mechanic for his coveralls, before recovering his old mask from Aaron's car. Deputy Frank Hawkins, who arrested Michael in 1978, tries to convince Sheriff Barker about the danger Michael poses after learning that he has escaped. Laurie also learns of Michael's escape and attempts to warn Karen, but Karen dismisses her concerns, urging Laurie to move on with her life.
Later that night, at a costume party, Allyson finds her boyfriend Cameron cheating on her and leaves with his friend Oscar. Meanwhile, while babysitting a boy named Julian, Allyson's best friend Vicky and her boyfriend Dave are attacked by Michael. Vicky sacrifices herself to protect Julian. Deputy Hawkins and Laurie overhear the incident on the radio and go over to the house. Laurie sees Michael, coming face-to-face with him for the first time in 40 years. Laurie shoots Michael in the shoulder before he flees.
Dr. Ranbir Sartain, Michael's psychiatrist, persuades Sheriff Barker to allow him to help in the hunt for Michael. Meanwhile, on the walk home from the party, Michael finds and kills Oscar but Hawkins and Sartain arrive just in time to rescue Allyson. Hawkins then tries to kill Michael but Sartain – who has become obsessed with Michael's enigmatic motivations – attacks and leaves Hawkins for dead, and it is revealed that he orchestrated Michael's escape in order to be able to study him "in the wild". However, Michael kills Sartain and Allyson flees from the scene. Michael then ambushes and kills two police officers arriving at the scene.
Michael drives the dead officers' car to Laurie's house, where she and Karen have gone to meet with Allyson. When Laurie's son-in-law Ray goes outside to greet who he believes are the two officers, Michael strangles him to death. Laurie manages to get Karen to safety before she engages in a showdown with Michael. Laurie severely injures Michael, but then he stabs her in the abdomen and pushes her over a balcony. When Michael goes to check Laurie's body, he finds it missing. Allyson arrives and calls out for her grandmother, luring Michael and giving Karen the opportunity to shoot him in the jaw. Laurie suddenly reappears and attacks Michael, trapping him inside the basement safe room with Karen and Allyson's help. The trio sets the house ablaze, and Laurie says goodbye to Michael before she begins to faint and lets her daughter and granddaughter quickly hitchhike a passerby vehicle to take her to the hospital. A final shot of the burning basement is shown, with Michael nowhere in sight. In a post-credits scene, Michael's breathing is heard, indicating that he survived.
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