This film is based on the 2000 novel "Blonde" by Joyce Carol Oates, which is a fictionalized account inspired by the life of Marilyn Monroe, not an actual biography. Oates insisted that the novel is a work of fiction that should not be regarded as a biography. Oates said that she didn't have anything to do with the making of this film, though once in a while, director Andrew Dominik would get in contact with her, and that she was given an almost-final cut in 2020 and she has praised the film ever since. The novel had been previously adapted into a two-part miniseries: Blonde (2001), starring Poppy Montgomery as Monroe.
Besides the blonde wig, Ana de Armas also wore blue contact lenses and dental prosthetics to look more like Marilyn Monroe.
Cuban actress Ana de Armas said in interviews that she spent nine months trying to perfect the voice and American accent of Marilyn Monroe. When the film was shown at test screenings in 2021, the audience complained about her accent still sounding Cuban. Director Andrew Dominik told ScreenDaily in February 2022 that there was "work involved" in post-production in making the actress "sound American."
Real footage from Marilyn Monroe's filmography is used in this movie, mixed with scenes recreated with Ana de Armas, who was placed in the films "All About Eve", "Some Like It Hot", "Don't Bother to Knock", "Niagara" and "Gentlemen Prefer Blondes". Andrew Dominik said that he initially didn't get permission to use footage from MGM films, so he had to shoot backup versions, like for the scene with Ana and Tony Curtis, he had to shoot that with an actor playing Curtis in case he couldn't get permission. Dominik got permission to use footage from those films after an MGM head got fired and was replaced by Mike De Luca, who gave him permission.
The character "Whitey" (Toby Huss) is inspired by Monroe's lifelong personal makeup artist Allan Snyder who served as a pallbearer at her funeral.