Make Your Home Among Strangers follows the classic literary model of a bildungsroman ,or coming-of-age story, but frames it in contemporary discourse about immigration reform and American identity. Lizet and her family are all either immigrants or descended from immigrants from Cuba, and are entangled in a national news story about the fatal capsizing of a raft of hopeful Cuban immigrants. Lizet's mother Lourdes is particularly embittered by the irony that the dangerous voyage was a desperate way of trying to bypass unfriendly, often illusory, paths to immigration set up by the United States. Her political activism borders on fanaticism, setting up a mother-daughter conflict with Lizet as she strives to adjust to the very different world of her homogenous (predominantly affluent and white) college.

Ultimately, Lizet learns that she can both pursue her dreams of becoming a biology researcher and find sympathy and solidarity with Cuban immigrant narratives. The novel therefore suggests that the modern American subject contains a multitude of cultural, ethical, and intellectual affinities that can be synthesized into a productive whole.