Ages ago, The Corvin Clan (also known as the Neo Vampires) confined their opponents, The Dracula Clan, underground. According to a prophecy, a child born nine seconds past 9:09 on September 9th, 1999 would possess infinite power and would save the Dracula Clan. Three children were born at that specific instant, but the only surviving one is a girl named Manami, who is unaware of her power or of the existence of vampires. When Manami becomes 22 years old, the power inside her will "mature" and be unleashed.

In the year 2021, hours before Manami's 22nd birthday, she is in a café with her friends. A vampire of the Dracula clan enters the café and kills every customer, in an attempt to take Manami with her, but she is soon herself killed by vampires of the Corvin clan, who are also looking for Manami. Manami flees from the café and she is eventually found by a vampire of the Dracula clan named K, who takes her with her. The two visit Manami's boyfriend, who turns out to also be a vampire, and is killed by K. Manami runs away from K and encounters Yamada, a psychotic vampire of the Corvin clan who takes her with him and explains to her who she is. K and other members of the Dracula clan find them, and the vampires engage in a fight for Manami. Eventually, Yamada wins and takes Manami with him.

The episode is split into two parts. The first part takes place in 2006, and depicts the childhood of M, one of the other, deceased girls born on the exact same instant as Manami. It is suggested that her parents are not truly her parents, but are simply paid by vampires to act like they are. Whenever they fail at properly parenting M, they are killed and replaced. By the end of the first part, M is a teenager with completely different parents than the ones she originally had. She starts bleeding and is approached by a stranger, who happens to be Manami. She dies trying to find Manami again.

The second part takes place in Transylvania in 2016. K, who is a normal human being, and her friend Noah, are exchange students in Romania. They encounter a Romanian girl who leads them through tunnels under the city to Corvin Castle, where a celebration is being held in honor of the day when Corvin slayed Dracula. As it turns out, the Romanian girl is a vampire, and she abducts K and Noah, taking them to Hotel Requiem, the lair of the Corvin clan, where they meet Yamada, his lover Elizabeth Báthory and her mother. The Corvin vampires feed on Noah, but are unenthusiastic about the taste of K's blood, and thus send her underground, as food for the Dracula clan. There, K becomes one of them.

A large amount of ordinary, "lonely" men and women have received mysterious invitations for an event, dubbed a "Coupling Party", to take place in Hotel Requiem. When they arrive at the Hotel, they are given large sums of money, and are promised even more money if they form a couple with another guest. K and her Dracula clan companions infiltrate the Coupling Party in search of Manami.

Yamada brings Manami to the hotel. Elizabeth's mother (who also raised Yamada), the owner of the Hotel, who is extremely old and disfigured, wants to drink Manami's blood when she turns 22, because it will restore her youth and make her live longer. The Corvin vampires cut Manami and feed Elizabeth's mother a small amount of her blood, which temporarily makes her young again. Noah, who has now become a Corvin vampire, feeds her own blood to Manami so her wounds can be healed.

It is revealed that the Prime Minister is actually Yamada's real father, who sold him over to the Vampires, thus causing Yamada's hatred for him and for the world at large. Manami attempts to escape, and ends up in the room where the Coupling Party takes place. There, she is spotted by K, but is escorted away by Noah, who reveals to her that she intends on helping her escape.

The guests are sent to separate rooms and instructed to create families for the vampires to feed on. It is revealed that Noah is betraying the Corvins and works with K to get Manami out of the Hotel. Manami, K and Noah successfully escape the Hotel, but K's companions stay behind and are killed by the Corvins.

The temporary effect of Manami's blood on Elizabeth's mother is dissolving, and as a result she is withering. As it turns out, the Hotel is actually her sister, and she fears that if she does not drink Manami's blood, she will too turn into a hotel, so she sends Yamada and Elizabeth to fetch Manami. They discover Manami is missing, but are unfazed, since they want Elizabeth's mother to die so Yamada can inherit the Hotel.

The Dracula vampires all feed on Manami, and as a result she also becomes a vampire. Master sends K, Noah and Manami to "handle things" in Japan, while he and the other Dracula vampires stay behind to fight in Romania. He promises K to marry her once she returns. On the way back to Japan, Noah confesses her love to K, but she does not reciprocate her feelings. Noah insists she follow them to Japan, but K refuses, and knocks her unconscious, leaving with Manami.

Elizabeth's mother comes back to life, but her body is microscopic, shriveled and doll-like. Elizabeth makes her mother her "pet", and thus, Yamada keeps his position as King of the Hotel. Yamada asks the guests if any of them do not believe the world has really ended; attempted escapee Gen does not, so Yamada lets him open the front door. Outside, Gen sees the world in flames, and nearly dies begging to come back, until Yamada forgives him and lets him in. After this incident, the guests are all convinced the world has really ended. Yamada orders them to gather in the hall.

Elizabeth and other Corvins find K and Manami. They take them underground to the Empress, the sister of Elizabeth's mother, whose body is the hotel. Manami is cut and her blood is fed to the Empress, with Yamada and Elizabeth also feeding on her. While she is being fed on, Manami takes full vampire form and escapes. K is imprisoned inside the walls of the hotel, which are full of old guests who did not start families or rebelled against the vampires, and are now forced to recreate and continually cut themselves to feed the living hotel.

In the aftermath of the battle, the few survivors clean up the blood, realizing that they have little time left to live now that the Empress is dead. However, two vampires claim that the hotel will survive, as they order a vampire chef named Cody to prepare meal for the humans. Manami wakes up, but has amnesia .

15 years later, the hotel is a peaceful and friendly place, where the few surviving vampires and humans live in harmony, as the guests eat the food prepared by Cody and agreeably offer their blood to be drawn as food for the vampires once a week. Manami still does not remember her past and is fully integrated into the society that has formed. We are introduced to Akari, a teenager who is the first and only human to have been born in the hotel.

Cody the chef visits the city to purchase food and meets a girl who he kidnaps and eats. As Akari and Cody are talking, she notices he smells of blood, which is odd since he claims he does not need blood and abstains from drinking the guests' donations. The two vampires visit K and determine that it may be time to replace her with Manami, as they deem K can't last much longer as the hotel's energy supply. Akari confronts Cody with the petals of the flower and he asks her to get rid of it. In the outside world, Cody is followed by a couple. We then see how he works as a bartender at nights to get the money necessary to buy food for the hotel.

Manami enters the room to find K. K tells Manami that one year earlier, Akari found K's room and regularly visited her since, with the two developing a friendship. Akari had now escaped through a hole in the wall in K's room in order to see the outside world. K bites Manami and awakens her memories. The police officers are captured and interrogated by the inhabitants of the hotel; they insist that the world outside still exists. The woman who found Cody's laptop confirms the officers' claims. Akari finds Cody in the outside world, and Cody confesses to killing people for blood whenever he left the hotel. The vampires eat the officers, as Akari returns to the hotel. The two vampires that maintained the hotel are crushed to realize that Yamada was lying to them and that the world hadn't really ended. Nevertheless, they and the guests resolve to continue life in the hotel as before and kill anyone who tries to escape. They hold a ceremony in which they are about to feed ancient blood to Akari so that she may replace K, but K and Manami intervene, rescuing Akari. K uses a sword to cut the chains on the front door, which opens. The living hotel is killed by the sunlight and the vampire staff members disappear. K is heavily injured by the sunlight, and dies in Manami's arms.