In Earth's future, a global crop blight and second Dust Bowl are slowly rendering the planet uninhabitable. Professor Brand (Michael Caine), a brilliant NASA physicist, is working on plans to save mankind by transporting Earth's population to a new home via a wormhole. But first, Brand must send former NASA pilot Cooper (Matthew McConaughey) and a team of researchers through the wormhole and across the galaxy to find out which of three planets could be mankind's new home.

Troubled Italian filmmaker Guido Anselmi (Marcello Mastroianni) struggles with creative stasis as he attempts to get a new movie off the ground. Overwhelmed by his work and personal life, the director retreats into his thoughts, which often focus on his loves, both past and present, and frequently wander into fantastical territory. As he tries to sort out his many entanglements, romantic and otherwise, Anselmi finds his production becoming more and more autobiographical.