"The Sisters Brothers" is a novel set during the California Gold Rush, following two brothers, Eli and Charlie Sisters, who work as hired guns. They are on a mission to track down a man named Hermann Kermit Warm, who has developed a formula for extracting gold more efficiently. As they travel through the rugged landscape, the brothers face various challenges that test their loyalty, morality, and the bond they share as siblings.
The narrative explores themes of violence, capitalism, and the complexity of brotherhood. Eli, the more introspective and sensitive brother, grapples with their violent lifestyle and begins to question their choices. In contrast, Charlie is more impulsive and embodies a hardened perspective on their line of work, which leads to conflicts between them.