Sarah (Asia Argento) becomes involved with a series of men who treat her and Jeremiah (Jimmy Bennett) poorly, and she uses them as an excuse to abandon her son. She disappears to Atlantic City with her boyfriend, Emerson (Jeremy Renner), and then abandons him; Emerson returns to their home and rapes Jeremiah. After a trip to hospital, Jeremiah's grandmother (Ornella Muti) takes him to a West Virginian radical Christian cult led by his grandfather (Peter Fonda). After he has been three years with the cult, Sarah returns to reclaim the 11-year-old Jeremiah (Dylan and Cole Sprouse).
Sarah's current lover, Kenny (Matt Schulze), a truck driver, eventually abandons them at a truck stop while Sarah is soliciting. Sarah realizes that if she is going to keep her men she cannot say Jeremiah is her son. She persuades Jeremiah to cross dress so he can act as her "little sister", and Jeremiah's cross-dressing evolves to include his mother's seduction techniques. After dressing up as a "baby doll" version of Sarah, Jeremiah/Sarah seduces Jackson (Marilyn Manson), his mother's latest man, who initially tries to rebuff the boy's advances, but then gives in. Sarah is furious with Jackson for giving in to the boy's advances and with Jeremiah for ruining her panties, and she takes Jeremiah and leaves.
Later, they are in a house where the basement houses a methamphetamine laboratory, which later blows up with Sarah's latest boyfriend inside. After fleeing, and while detoxing from methamphetamine, Sarah is convinced that everyone is after them and that only certain foods are edible (mainly chips and soda). She convinces Jeremiah that if they eat anything but those foods, they will be poisoned which leads them to a failed attempt to shoplift at a grocery store; afterwards, Jeremiah finds a hamburger to eat from a dumpster. His mother, in a state of "meth psychosis", is convinced the food he ate was poison, and makes him drink ipecac in order to make him better and rid him of any "poisons".
Jeremiah wakes up in the hospital with his grandmother beside him. She tells him that Sarah is in the psychiatric ward. Later that night, Sarah collects Jeremiah from his hospital room, and, rather than have him go back to the cult, she clutches his hand and they walk away in hospital gowns. The final scene is of Sarah and Jeremiah driving away.