Once, there was an explosion. Lonesome souls of the dead began to manifest in the physical world, reaching out to the living. However, the connection they seek triggers a massive explosion that eradicates anything of this world, a catastrophic phenomenon known as the Death Stranding. When these events occurred simultaneously across the globe, nations and civilization itself were wiped away, leaving the few survivors isolated, withdrawn, and without connections to one another. As humanity stands at the brink of extinction, a legendary porter sets out to transport both cargo and the wishes of its senders, attempting to reconnect people in the hope that they might still be saved.

Somewhere in North America, just as Sam Bridges walks across the continent to save what remains of America, four other individuals are also trying to deal with their isolation in their own way. An old man seeks salvation through means that exist outside the connection advocated by Bridges and his organization. A female warrior tries to kickstart a world of constant, endless fighting. A boy holds a deep grudge against Bridges. A girl embraces her loneliness rather than fighting against it. These characters, currently known only as the someones, find their fates and hopes converging on the precipice of the end of humanity and the world. As another story of the Death Stranding begins, a new explosion is coming.

This original narrative branches off from the established universe of the Death Stranding video games. Rather than retelling the story of Sam Porter Bridges, the series follows these four distinct individuals whose paths collide against the backdrop of a shattered America. The boy with a grudge and the female warrior appear prominently in key art as the central protagonists of this new tale, their eventual connection driving much of the narrative. While Sam Bridges is mentioned in the synopsis as walking the continent at the same time, the series focuses on how ordinary people cope with the apocalypse in different, sometimes conflicting, ways. The production is described as following in the footsteps of the original game in spirit and ideas, depicting the world of Death Stranding through a bold yet subtle touch with top-class hand-drawn animation.