Holm is especially well known for her collaborations with her brother Matthew Holm, who illustrated the Babymouse and Squish graphic novel series, among other works. In several interviews, Holm mentions drawing inspiration from her own family history when writing historical fiction novels, a process which informed her first science fiction novel, The Lion of Mars (2021). In an interview for The Horn Book Inc. with Roger Sutton, Holm explains:

My first book, Our Only May Amelia, was about my Finnish-American family in Washington State. As I started thinking about what their lives were like, and talking to my family about it, they honestly may as well have gone to Mars when they left Finland. They never returned. It was a one-way trip, which is true for so many immigrants. [When] they arrived in America it was obviously very difficult, and I started thinking of their experience as being parallel to living on Mars. Instead of settling Mars in a high-tech, shiny way—a glass-encased bubble on the surface—I thought the technology would get us there, but living there would be more akin to what it had been like for my family (Sutton, Roger. “Jennifer L. Holm Talks with Roger.