A lonely customer service expert, who leads a numb existence because he perceives everyone as identical, finds himself feeling rejuvenated when he meets a unique and lively woman. Will his life be changed forever, or will he return to his melancholy state?
In 2005, customer service expert Michael Stone travels to Cincinnati, Ohio to promote his latest book at a convention in a hotel. He is distant from everyone around him, whom he perceives as having an identical face and voice, including his wife and son. Michael practices his talk in his hotel room, but is haunted by the memory of an angry letter from his old flame, Bella, whom he abruptly left years ago.
He arranges to meet her in the hotel bar; still angry, she is outraged by his invitation to his room and storms out. Going for a walk, Michael mistakes an adult toy store for a children's toy store and tries to buy something for his son, but is fascinated by a Japanese animatronic woman.
After taking a shower, Michael hears a female voice. He rushes from his room to find its owner: an insecure young woman named Lisa Hesselman attending Michael's talk with her friend. Enraptured by her unique appearance and voice, he invites both women for drinks at the bar. Afterwards, to Lisa's surprise, Michael invites her to his room. Despite her claims that she is not special, Michael finds her captivating, admiring the facial scar she conceals with her hair. He encourages her to sing Cyndi Lauper's "Girls Just Want to Have Fun" and tell him about her life. Declaring her an "anomaly", he nicknames her "Anomalisa". They become intimate and have sex.
Michael has a nightmare in which his face falls apart and the identical people of the world pursue him, claiming they love him and that he and Lisa cannot be together. The dream inspires Michael to propose that he and Lisa run away and start a new life. She agrees, but her eating habits during breakfast annoy him, and her voice and face begin to transform into everyone else's. During his convention talk, he suffers a breakdown, confessing that he has no one to talk to and ranting about the American government, alienating the audience.
Michael returns to his Los Angeles home. He gives his son the Japanese animatronic woman as a gift, which nonplusses him. Michael's wife has arranged a surprise party, but he is unable to recognize any of the attendees, angering her. Michael sits alone on the stairs as the animatronic woman sings 'Momotarō's Song', a Japanese children's song. Lisa writes a letter to Michael, saying she hopes they will meet again. Lisa's friend, sitting beside her in the car, has her own face.
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