Luiselli was in part inspired by the ongoing American policy of separating children from their parents at the Mexico–United States border.

[3] The novel details a cross-country journey from New York to Arizona in a car by a husband and wife, Mama and Papa, and their children, "the girl" and "the boy," both from previous relationships.

[4][5] The novel incorporates fragments from the poetry of other poets, including from poems by Anne Carson, Galway Kinnell, and Augusto Monterroso.

The boy eventually believes that if he and the girl lose themselves they will be able to find Manuela's children and their parents, who will go searching for them, will be able to retrieve all four of them.

[15] On the May/June 2019 issue of Bookmarks, the book received (4.0 out of 5) stars, with the critical summary saying, "Like her earlier work,” concludes NPR, “[the novel is] a remarkable feat of empathy and intellectuality that once again showcases Luiselli’s ability to braid the political, historical, and personal while explicitly addressing the challenges of figuring out how to tell the very story she’s telling".

[19] In the second season of The White Lotus, the character of Harper Spiller (played by Aubrey Plaza) reads Lost Children Archive.