Theater director Caden Cotard (Philip Seymour Hoffman) is mounting a new play. His life catering to suburban blue-hairs at the local regional theater in Schenectady, New York is looking bleak. His wife has left him to pursue her painting in Berlin, taking their young daughter Olive with her. His therapist, Madeleine Gravis is better at plugging her best-seller than she is at counseling him. A new relationship with the alluringly candid Hazel has prematurely run aground. And a mysterious condition is systematically shutting down each of his autonomic functions, one by one. Worried about the transience of his life, he leaves his home behind. He gathers an ensemble cast into a warehouse in New York City, hoping to create a work of brutal honesty. He directs them in a celebration of the mundane, instructing each to live out their constructed lives in a growing mockup of the city outside. The years rapidly fold into each other, and Caden buries himself deeper into his masterpiece. As he pushes the limits of his relationships, both personally and professionally, a change in creative direction arrives in Millicent Weems (Dianne Wiest), a celebrated theater actress who may offer Caden the break he needs.