The Last Seduction is a story about a sociopath femme-fatale, Bridget Gregory, who steals a bag of money ($700,000) from her drug-dealing husband Clay. Bridget drives off headed to Chicago when she happens to stop at a small town, Beston, and meets Mike, who is back in town after a whirlwind marriage and divorce in Buffalo. The two immediately hook up. Bridget is just looking for sex while Mike is trying to find a way out of the small town.
Meanwhile, drug dealer Clay gets his thumb broken by the loan shark who is looking for repayment for his loan. Clay, with the help of a private detective, frantically searches for his plotting wife and the money. In the small town Bridget changes her name and gets a job at the same insurance company Mike works for. (Her alias "Wendy Kroy" is derived from "New York" spelled backwards; Clay knows of her penchant for backwards spelling and writing and eventually tracks her down through this alias).
When Mike tells her how to find out if a man is cheating on his wife by reading his credit reports, Bridget invents a plan based on selling murders to cheated wives. She then pretends to travel to Florida to murder a cheating husband (when she in fact went to Buffalo to meet Mike's ex-wife, Trish). She shows Mike the money she stole from Clay to convince him she has taken a cut from the life insurance payout from the new widow as payment for the supposed killing. She tells him she has done it so they can live together from the proceeds, then persuades him that he must also commit a similar murder so they will be even, and to prove that he loves her.
She tries to talk Mike into killing a tax lawyer cheating old ladies out of their homes. At first he rejects the idea, then later agrees after receiving a letter from his ex saying she is moving to Beston. But the letter was really written by Bridget to change his mind.
Mike goes to New York and breaks into the apartment of the attorney, who in reality turns out to be Clay. After Clay is tied up by Mike, he manages to work out what is happening when Mike mentions her alias, and convinces him of the truth by showing him a photo of himself and Bridget together.
They then hatch a plot to double cross her, but she turns the tables by killing Clay herself. She tells a stunned Mike to rape her. When he refuses, she tells him she knows the truth about Trish who is a transsexual. She then tricks an enraged Mike into having rough sex with her while she has 911 on the line. Mike ends up in jail facing rape and murder charges while she escapes with the cash.