The movie is focused on a screen writer who tries to adapt a book with a convoluted plot into a movie. The main character, Charlie Kaufmann, is a very depressed and self-deprecating human that has problems with social behavior. His twin brother Donald, also played by Nicolas Cage, a weird character, moves in with him and decides that he too wants to be a screenwriter.
The movie wraps on as the main character, Charlie, tries to marry his own ideals of book adaptation and the material. However, the book, "The Orchid Thief" proves to be so non-sensational that the narrative is impossible to write. This lunges Charlie into a fit of depression and writer's block. By now, the time he had to write the script has long passed and he sees the time to face his boss in this situation, Susan Orlean, played by Meryl Streep has come. However, his squeamish personality, paired with the surprising news that his twin brothers weird script is selling for millions, stop him in pursuing the meeting. Charlie Kaufmann then decides to visit the same screenwriting course his brother attended to ask Robert McKee, played by Brian Cox, for some tips. The situation ends with Charlie pleading his brother Donald to help him in New York.
Donald now decides to help by interviewing Orlean, pretending to be Charlie. Something seems fishy to him and so he decides to take his brother and follow her to Florida. The twins find her meeting John Laroche, played by Chris Cooper, her secret lover and protagonist of the book. They discover that the orchid in question is used by an Indian tribe to create a hallucination inducing drug. And while Charlie is watching Orlean and Laroche have sex and take the drug together. Discovering that they were watched, Orlean wants Charlie dead.
At gunpoint she forces Charlie to drive with her deep into the bayou, where she plans to shoot him. However, the twins manage to escape for a while, till they are discovered by Laroche, who hits Donald with a bullet. Fleeing again a car accident causes Donald to die. Charlie sees no other option but to flee again into the swamp. Being discovered again by Laroche he fears for his life. However, John becomes the next meal for a hungry alligator.
The movie ends with Orlean being arrested and Charlie finally has a relationship with his mother again. After admitting his love to a Amelia, played by Cara Seymour, he manages to finish the script, with the final wish that Gerard Depardieu should play him.
