On the Road centers on Veneno, a gay hitchhiker surviving through sex work, and Muñeco, a married truck driver, as their wary companionship evolves into an intimate, sexually charged relationship across Mexico’s highways. The film portrays their bond with complexity and moments of genuine tenderness while navigating external pressures of machismo and violence. It affirms queer desire and connection as valid amid harsh circumstances.

On the Road centers on a middle-aged truck driver who maintains a distant marriage and rarely sees his children while developing an increasingly intimate relationship with a young male drifter who has no family ties. The narrative frames family life as physically and emotionally separated from the characters' transient existence on the road.