Numerous characters from the intoxicating world of The Queen of the Damned have graced the pages of the Vampire Chronicles before. Among these familiar faces are the enigmatic Lestat, the contemplative Louis, the stoic Narius, the fierce Gabrielle, the charismatic Armand, and the enigmatic Nael. Akasha and Enkil made their striking debut in The Vampire Lestat (1985), with Akasha taking center stage in The Queen of the Damned. This narrative also ushers in a cast of fresh faces: the insightful Jesse (Jessica), the mystical red-haired twins Maharet and Mekare, the curious Daniel, and Khayman, an ancient Egyptian who shares the origins of vampirism with Maharet and Mekare. Daniel, readers will recall, was the inquisitive voice in Interview with the Vampire (1979).

Awakened from her age-old slumber by Lestat's electrifying music and rebellious antics, Akasha emerges with a radical vision—to reshape the world. Her utopia is one populated largely by empowered women, with a scant presence of men until they evolve beyond their inherent aggression. In her fervent quest, she obliterates entire villages of men and any vampires daring enough to defy her. Yet, she spares Lestat and his companions, deeming them among her chosen few. When Lestat condemns her brutal strategy, she challenges him, pointing to humanity’s history of oppressing women: "Don't you think the peoples of this earth have limited in the past their female children? Don't you think they have killed them by the millions because they wanted only male children so that those children could go to war?" Akasha envisions a new era of tranquility, one she believes only women can usher in: "We shall see for the first time since man lifted the club to strike down his brother, the world women could make and what women have to teach men. And only when men can be taught, will they be allowed to run free among women again."

Among the venerable vampires stands Maharet, keeper of the chronicles of the Great Family. This ancient vampire exudes such benevolence that her true nature is often forgotten. Her noble quest revolves around safeguarding her family's legacy and reuniting with her long-lost twin, Mekare. Maharet embodies the timeless virtues of family, transcending race, nationality, and creed. Through her, Rice suggests that our quest for love, and our faith in its endurance, will outlast even the most enduring of religions: "we can search for love and maintain it and believe it ... this age has demonstrated that the belief in the value of love will endure after religions have passed away."

Once more, Lestat takes a pivotal role, stirring the pot with his unpredictable and rebellious spirit. Just as in The Vampire Lestat, he is the storm that sets events into chaotic motion, further exposing the vampire world by flaunting its existence, much to their chagrin. Akasha seeks him as a partner in her destructive vision to thin the human male population and silence dissent among vampires, while others view him as a threat to their secrecy, thereby inciting significant conflict. In an interview, Rice shared that her vampires are "perfect metaphor for people who drain us dry, for our fear of the dead coming back, for the outsider who is in the midst of everything and yet feels monstrous and completely cut off." Moreover, her vampire characters eloquently voice her commentary on global issues, the diminishing relevance of religious doctrines, and the fading notion of gender-defined roles—ideas that pulse at the heart of her novel.