The sound of a nu metal band arouses the vampire Lestat de Lioncourt from a lengthy slumber, and he proceeds to take over as their lead singer. Achieving international success with the ensemble, which he names The Vampire Lestat, and having revealed the existence of vampires, he taunts his own kind during an interview to advertise his first and only live concert.
Jesse Reeves, a researcher for the paranormal studies group Talamasca, is intrigued by his lyrics upon hearing one of his songs play on TV and tells the other members her theory that he really is a vampire. Her mentor, David Talbot, explains to her they already know of his identity and donates Lestat’s journal that he recovered so that Jesse can read it, but warns her against pursuing Lestat.
In the journal, Lestat recalls that in the winter of 1788, he was brought to a Mediterranean island and vampirized by Marius de Romanus, formerly a talented painter, and his violin playing awoke Akasha, the first vampire. Increasingly intrigued, Jesse tracks Lestat down to a London vampire club called The Admiral’s Arms, where he saves her from three vampires and confronts her about Marius.
Visiting Lestat in Los Angeles, Marius warns him that the other vampires will not tolerate his flamboyant public profile; he reveals that Lestat’s music has awakened Akasha and unsuccessfully implores him to cancel his concert. Meanwhile, Akasha arrives at the coven, looking for Lestat. After the vampires reveal their plan to kill him at his concert, she torches the club and kills all the vampires inside.
Arriving in Los Angeles, Jesse gives Lestat his journal back and asks him to show her what being a vampire is like. He scoffs at the idea, but she convinces him to spend time with her. She later enquires if he can convert her, expressing her desire to be with him and know everything he does.
Lestat is attacked by a group of vampires at his concert in Death Valley, and Marius aids him in defeating most of them until Akasha arrives and promptly carries Lestat with her to her home on an island resort. During their period of sexual intercourse, he becomes spellbound and subservient to her.
Jesse awakens in the house where she lived as a child, in awe at the sight of her aunt, Maharet, who later reveals herself as a member of the Ancient Vampires. Fearing Akasha’s plans for world domination, the Ancient Vampires decide to destroy her by draining her blood. However, they believe that whoever drinks her last drop will not survive.
Akasha confronts the Ancient Vampires and interrupts their meeting, with Lestat, empowered by her blood, accompanying her. When they refuse to side with her, Akasha commands him to kill Jesse, seeing her both as an enemy due to being Maharet’s descendant and as food.
He ostensibly obeys, but after drinking Jesse’s blood, comes to his senses and is released from Akasha’s controlling influence. He demands his “crown,” and as Akasha openly offers him her arm to feed on, he then turns on her and, aided by the Ancients, begins to drain her blood, diminishing her power.
Now a vampire, Jesse visits David, accompanied by Lestat, and returns the journal. When David nervously asks her about life in her current status, Jesse offers to vampirize him, but he declines due to his age. Jesse then bids David farewell and goes to embrace him, but he fearfully rejects the embrace.
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Sensing his hesitation, Jesse looks hurt but nods in understanding and leaves with Lestat. Marius then enters David’s office, aware that David has obsessed over him for many years, and politely greets him. Lestat and Jesse walk hand in hand, among mortals, into the night.
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