The series explicitly centers on a complex, passionate, and often toxic gay romance between Louis and Lestat, alongside an unconventional queer family dynamic. While depicting significant abuse and tragedy, the narrative explores their identities and love with depth and dignity, affirming their worth within the story's fantastical and violent context.

Louis de Pointe du Lac and Claudia, central characters canonically established as white in the original novel and previous film adaptation, are portrayed by Black actors in the 2022 show, constituting a race swap.

The series consistently portrays Christianity, particularly through Louis's perspective and the societal backdrop of early 20th-century New Orleans, as a source of hypocrisy, oppression, and moral rigidity. It highlights the church's failure to address societal injustices and its condemnation of those who deviate from its norms. The narrative offers no significant counterbalancing positive portrayal of the faith.