Like Shan's previous series, Zom-B is notable for exploring themes of racism, xenophobia, and the sociological concept of "us and them".

The series also explores B's own connections to the instigators of the apocalypse, including the Owl Man and a mysterious group of babies.

[3] The majority of novels in the series are written as concluding with a cliffhanger leading to the subsequent book, structured in a manner similar to television serials.

[5] The decision to leave B's gender initially ambiguous was explained by Shan to allow the reader to question their own assumptions and biases with regards to the way B acts and how women "should" be written in works of fiction.

[16] In March 2021, Susan E. Connolly was announced to be attached as the lead writer on the project, with The Electric Shadow Company releasing a teaser image depicting a blood-spattered B Smith opposite her best friend Vinyl to their website.