Elisabeth is a television star from an aerobic show. The day she is fired due to her aging body, she sees her advertising posters being taken down from the streets of the city when suddenly, she suffers an accident that will take her straight to the hospital. There, she is given a USB with information about a strange product called 'The Substance' and its supplier, with whom Elisabeth contacts. He explains to her that it is a serum that, when injected, creates a younger and more beautiful version of oneself that is born from the spine, and that both versions remain connected as one.

After giving it some thought, Elisabeth contacts the producer to sell her the serum so that a young version of her can be born, allowing her to succeed again on television. This new girl adopts the name Sue, who receives the order from the supplier that she must inject a serum to stabilize Elisabeth while she is unconscious, as they cannot both roam the world at the same time.

This film is directed and written by Coralie Fargeat and stars Demi Moore ('Ghost') and Margaret Qualley ('Kinds of Kindness') in the roles of Elisabeth and Sue, respectively. The cast also includes Dennis Quaid.