The Protagonist defiles the paintings at an art gallery at Jeanette's request. The Protagonist then defeats the Blood Guardian that appears shortly afterward. The Protagonist returns to The Asylum, finding Therese furious. Therese tasks the Protagonist with finding Jeanette at a nearby diner.
The Protagonist goes downtown and is knocked out by a Sabbat attacker. Three Sabbat consider harming the Protagonist further, but Nines Rodriguez prevents this from happening. One of the Sabbat attack Nines anyway, causing the Sabbat attacker to be killed. Nines then tells the Protagonist to meet him later.
The Protagonist meets with LaCroix, who tells the Protagonist to investigate the Elizabeth Dane.
The Protagonist investigates the Elizabeth Dane. The ship manifest is taken and the Ankaran Sarcophagus is found by the Protagonist.
LaCroix has a meeting with several other primogens concerning the disappearance of Dr. Alistair Grout as the Protagonist returns to report to LaCroix. LaCroix tasks the Protagonist with solving the mystery of Grout's disappearance.
The Protagonist arrives at Grout's Mansion. Ming Xiao, disguised as Nines, is briefly encountered by the Protagonist leaving the mansion. The Protagonist defeats various ghouls roaming the mansion and solves various puzzles, eventually entering Grout's inner sanctum. Grout is found dead in his bedroom by the Protagonist.
The mansion is set on fire by Grünfeld Bach as the Protagonist leaves in an attempt to kill Dr. Grout. Both manage to escape the burning mansion.
The Protagonist reports to LaCroix on the events at Grout's mansion. LaCroix tells the Protagonist that seeing Nines at the mansion may mean war with the Anarchs. LaCroix tasks the Protagonist with taking the Ankaran Sarcophagus.
The Protagonist finds the tape hidden in a graveyard. The tape is brought to Isaac, and the Protagonist and Isaac watch the tape together. Isaac notes that the tape went into circulation when the Nosferatu ceased contact - he tasks the Protagonist with finding a complete copy.
The Protagonist discovers a keycard to access Death Mask Productions offices. Upon arrival, the Protagonist is attacked by monsters used in the snuff film. The Protagonist takes the complete snuff film tape and brings it back to Isaac. Watching the complete tape, Isaac deduces that the film was shot at 609 King's Way.
The Protagonist goes to 609 King's Way and defeats Andrei for the first time. Andrei escapes the encounter as the Protagonist enters the Nosferatu Warrens.
After fighting past the various monsters inside the Warrens, the Protagonist enters the Nosferatu Warrens, encountering Gary Golden, who reveals that the Sarcophagus has been sold, but will only reveal the buyer if the Protagonist finds Barabus in Chinatown.
The Protagonist goes to Chinatown and receives permission to operate in the Kuei-jin domain from Ming Xiao. Upon leaving the Golden Temple, Kiki is kidnapped by the Tong. Wong Ho recruits the Protagonist to rescue Kiki in exchange for his help.
The Protagonist enters the Glaze to search for Johnny. Upon reaching Johnny's office, Johnny is provoked into attacking the Protagonist by The Mandarin. After shooting the Protagonist, the Mandarin reveals the vampiric nature of the Protagonist, forcing the Protagonist to kill Johnny. The Protagonist then goes to the Fu Syndicate to discuss the terms of Barabus's release at the Mandarin's invitation.
The Protagonist is taken captive by the Mandarin and run through several tests to determine Cainite weaknesses. In the final test, the Protagonist blows up fuel tanks, destroying the observation windows and forcing the Mandarin to run. The Protagonist kills the Mandarin and frees Barabus, who reveals that the data the Mandarin collected must be destroyed.
After destroying the data and leaving with Barabus, the Protagonist is contacted by Gary, who reveals that the Ankaran Sarcophagus is held by the Giovanni at the Giovanni Stronghold.
The Protagonist enters the Giovanni Stronghold and enters the catacombs. After fighting past the zombies inside, the Protagonist enters the catacombs and encounters The Chang Brothers. The brothers are fought and killed by the Protagonist; the Protagonist brings the Ankaran Sarcophagus to LaCroix shortly afterwards.
LaCroix tasks Beckett and the Protagonist with finding a way to open the sarcophagus. Beckett informs the Protagonist that Dr. Johansen may know a way to open the sarcophagus, who is being held at the Society of Leopold Monastery.
The Protagonist enters the Monastery and mortally wounds Bach. Shortly afterwards, Johansen is found. When moving to leave the Monastery, Bach triggers an explosive to destroy the monastery. The Protagonist escapes before the monastery is destroyed.
The Ventrue Tower is attacked by the Sabbat. LaCroix orders the Protagonist to defeat the Sabbat leadership in LA.
The Protagonist raids Hallowbrook Hotel and successfully kills Andrei. Upon leaving, the Protagonist encounters Ming-Xiao, who reveals that she killed Grout. She also says she has the key to the sarcophagus before leaving.
The Protagonist returns to LzCroix and reveals the location of the key. LaCroix declares an end to the blood hunt against Nines in order to focus against the Kuei-Jin. The Protagonist is rodered to go to Nines and propose an alliance against the Kuei-Jin.
Beckett warns the Protagonist to not open the sarcophagus before presumably leaving LA.
The Protagonist learns that Nines is hiding in Griffith Park from Damsel. The Protagonist goes to the Park to find Nines, but the Park is set on fire. Two wereolves are drawn out - one is defeated by Nines, while the other is encountered by the Protagonist. The Protagonist uses a cablecar to leave the park and escapes to the Santa Monica haven with Smiling Jack.
The Protagonist goes to Ventrue Tower to resolve the issue of the Ankaran Sarcophagus and LaCroix. If the Protagonist supports LaCroix, both die; otherwise, the faction the Protagonist supports will take control of LA.