The Marrow Thieves takes place in a not-too-distant future in which the climate crisis has worsened signficantly. In this dystopian world, there are constant, torrential rains and many lands are no longer habitable. Half of the human population has died, and most have lost the ability to dream, leading to widespread madness. Only Native people still have the ability to dream, and the Canadian Government sets out to steal this ability through the extraction of Native people's bone marrow, which is where their dreams live. To do so the government creates a system of schools, based on the old residential boarding school system.
French and Mitch are Indigenous Métis brothers who have lost their father and mother. Recruiters surround their hideout and Mitch sacrifices himself so that French can escape. French wanders into the woods where a group of Indigenous people led by a man named Miigwans rescues him. Together they travel northward, where Native peoples are said to be doing better. Miigwans teaches French and the other youngsters about the history and present of the destruction of the earth and the oppression of Indigenous people. Eventually, he explains that marrow harvesting is a process that kills its victims. He also teaches the youth skills like hunting so they can survive in the wilderness. Meanwhile, a quiet old woman named Minerva teaches the group some of their traditional language and culture.
As the group travels on they encounter new members and lose others. Rose joins the group, and she and French eventually start a romantic relationship. The group encounters two Native traitors who work for the Recruiters, and this leads to the death of their youngest member, RiRi. Shortly thereafter, Recruiters take Minerva in the middle of the night. The group decides to travel toward a city named Espanola, where there is said to be an Indigenous resistance movement, in the hopes of getting information that will help them rescue Minerva.
One night, a group of masked and armed people captures them. At first, they are hostile. But they turn out to be members of the Indigenous resistance group and they invite Miigwans and the youth to their camp. There French reunites with his father, who has helped to re-establish the Native Council at the camp. Members of the camp explain that Minerva managed to destroy the Recruiters' marrow-harvesting system by singing a song in her native language. The song was comprised of all her dreams, also in her native language, which she recorded over the years. Together the groups plan to rescue Minerva when her convoy passes a nearby highway. The group nearly manages to save Minerva, but at the last minute, a driver shoots her to death. The devastated group buries Minerva and travels ten days before establishing a new camp. There Rose decides to leave and French runs after her. But before they get far they must join the others to inspect a group of strangers that the scouts have detected near the camp. Among the strangers is Isaac, Miig's half-Cree husband who he believed he had lost to the schools. The novel ends with their emotional reunion.
