Chased by an unseen force, Duncan Hayslip desperately runs through the streets and into his mother's home, urging his wife, Sarah, to seek refuge in the basement as the creature pursues him, breaking down the door behind him.
123 Hours Earlier - A sonogram reveals a peculiar polyp lodged within Duncan's digestive tract. Dr. Yeager explains that this unusual growth is likely a consequence of poor stress management and refers Duncan to a therapist, Highsmith. As the days unfold, Duncan faces a tough change at work when his boss, Phil, reassigns him from Accounting to Human Resources to handle job terminations. To add to his discomfort, Phil pushes Duncan into an office located in the men’s room, where he has to coordinate with Allistair. A session with Highsmith produces no helpful results.
During dinner with Duncan's lively mother, Beatrice, and her much younger husband, Bobbi, the atmosphere is further charged as Beatrice tries to encourage her son and Sarah to conceive by inviting fertility specialist Dr. Tip. Just when Duncan thinks he can catch a break, Allistair calls him in a panic—an important file has been accidentally deleted.
Retreating to the bathroom to manage his escalating anxiety, Duncan finds himself in a seemingly unbearable situation when a creature emerges from his body, leaving him unconscious. This sinister force soon wreaks havoc at his office, killing Allistair before it returns to Duncan. The local KRAC news, however, misattributes this death to a rabid raccoon, leaving Duncan even more puzzled about the strangeness surrounding him.
When he reports to work, Duncan has to begin the painful process of letting colleagues go under Phil's direction. Meanwhile, Dr. Tip pressures him through voicemail to visit the fertility clinic. Amidst haunting dreams, Duncan imagines the creature attacking Dr. Yeager during a colonoscopy.
In a second session with Highsmith, Duncan undergoes hypnosis, leading to a shocking discovery: the creature escapes his body and leaps out of the window. Highsmith parallels Duncan's struggles to an ancient myth surrounding the anus, suggesting the entity surfaces only when Duncan finds himself under extreme stress—potentially a manifestation of his subconscious.
After the creature kills Dr. Tip in a grim alley encounter, Duncan calls it by the name Milo, leading to a strange bond between man and creature that sees Milo crawl back inside him. The following day, Duncan uncovers a serious discrepancy at work, only for Phil to coax him into committing fraud for cover-up. Reporting on the death of Dr. Tip as another raccoon incident, the media creates a bizarre narrative.
During yet another therapy session, Duncan delves into his tumultuous relationship with his father, Roger. Encouraged to reconcile, Duncan visits his estranged father, who outright rejects the idea of therapy. Despite this, due to overwhelming stress, Milo re-emerges while Duncan is at Roger's outhouse, where Duncan persuades him to return inside by promising to take care of him.
The tension escalates as federal agents swoop in to seize the office's records. Duncan confronts Phil about the situation, only to learn about his lost investment in the company. In a moment of desperation, he lets Milo take control, resulting in Phil's gruesome fate in an elevator.
When Sarah reveals she’s pregnant, Duncan grapples with the news, already fraught with the loss of their finances and the death of Phil. The weight of these revelations pushes him out of the house, leading to a unique connection between him and Milo as they navigate Duncan's newfound solitude.
Duncan eventually convinces Roger to join him in a therapy session with Highsmith. However, the encounter spirals out of control, leading to the emergence of creatures from both men—Milo attacking Roger's demon, named Ralph. As Milo becomes aware of Sarah’s pregnancy, he reemerges, prompting Duncan to race to his mother's house to protect her and the unborn child.
In a thrill of activity, Duncan arrives at the opening scene, urging Sarah to hide in Beatrice's convoluted basement. The climactic chaos unfolds as Milo breaks into the house, launching through the garbage disposal pipes. An ensuing struggle sees Milo attacking Sarah; yet, Duncan rushes to her aid. Party guests, armed with tiki torches, confront the demon outside.
In a ferocious battle, Duncan manages to sever Milo’s limbs with a decisive chop. Beatrice reveals she was aware of the hereditary nature of the colon creature, yet kept it a secret. In an act of reconciliation, Duncan makes peace with Milo, who returns to his host. He then turns to Sarah, offering his apologies.
Finally, Duncan opens his own financial consulting firm, but there are lingering consequences—Roger now lives as an invalid, and Sarah's pregnancy culminates in the revelation that their unborn son carries a creature of its own, hinting at a twisted hereditary legacy yet to unfold.
