Adapted from Edward Ashton's sci-fi novel Mickey 7, the thought-provoking satire tells the story of Mickey Barnes, portrayed by Pattinson, who is forced to sign a dreadful contract and join a space expedition with the goal of discovering a new colony for humanity. The contract assigns Barnes as the "expendable", meaning his memories are scanned to create clones in the event of his death during dangerous missions, such as testing the air on an alien planet without proper protection.
After being killed 16 times, the 17th Barnes, known as Mickey 17, falls into an icy cave and is presumed to have been eaten by worm-like alien creatures. However, he miraculously survives and returns to the ship, only to be shocked at the sight of Mickey 18, his replacement, already created. This puts them both in a deadly predicament, as the laws of their futuristic Earth dictate that such duplicates must be eliminated.