The novel takes place primarily on the Little No Horse Ojibwe reservation in North Dakota. The characters include Native American, Euro-heritage, and mixed-race/heritage people who live and work on or near the reservation. As the action spans about 80 years, there are several additional settings and some minor characters connected with the other times and places.

Louise Erdrich had previously created multi-generational sagas involving several of the families featured in The Last Report…. Here we learn what happened later to one of the main characters of her novel Tracks, the mentally unstable and ultimately homicidal Pauline Puyat. Transformed into Sister Leopolda, her devout deeds have not merely become the stuff of legend but are considered miracles. A substantial part of the plot involves the Vatican emissary, Father Jude Miller, who is investigating the miracles to see if Leopolda should be canonized, for the last report of the title.

Secrets in past lives are not confined to Sister Leopolda, however. Much of the story revolves around Father Damien Modeste, who had begun life as a woman and had also previously been a nun. Feeling compelled to abandon her old life, and coincident with the real Damien’s death, Agnes/Sister Cecilia assumes his identity. Making his way to the Little No Horse reservation, Damien begins a new life of service to the area’s Native peoples. Not temperamentally suited to proselytizing, Damien comes to empathize with their economic poverty and spiritual insights, even as he confronts his own duplicity.

Continuing from Tracks as well is one of Erdrich’s most enduring characters, Nanapush; in this novel we see him at different phases, not only as an elderly man. With a zest for life often masked by cynical commentary, and the ability to see through his fellow humans’ foibles, Nanapush befriends Damien and brings a humorous element to circumstances that might otherwise seem gloomy. While he primarily represents the Native American trickster figure, Erdrich fleshes him out into a three-dimensional person.