Charlie Kaufman (NICOLAS CAGE) is a neurotic and self-doubting screenwriter who's been assigned to adapt author Susan Orlean's (MERYL STREEP) novel, "The Orchid Thief," into a screenplay. Yet, he's having trouble doing so, especially when pressured by studio executive Valerie (TILDA SWINTON) and his agent, Marty (RON LIVINGSTON), to complete it as soon as possible.
It doesn't help matters that his more freewheeling twin brother, Donald (NICOLAS CAGE), has decided to take up screenwriting as well. Having attended classes by screenwriting guru Robert McKee (BRIAN COX), Donald turns out to have a knack for it despite doing everything that Charlie believes is wrong from an artistic standpoint. Unlike his brother, Donald has no problem with the ladies, whether it's Amelia (CARA SEYMOUR) or make-up artist Caroline (MAGGIE GYLLENHAAL).
As Charlie attempts to write this story that he believes isn't filmable, we see flashbacks of Susan at work at the New Yorker writing her book, as well as ones even further back where she interviews and eventually falls under the spell of her titular subject, John Laroche (CHRIS COOPER), and his passionate lifestyle and mindset.
With time running out, Charlie tries various ways of finishing his script, ranging from finally meeting Susan to actually writing himself and his brother into the story.