Juliette returns to Shanghai after spending four years at school in New York City. When she returns, she takes her place as the heir to the Scarlet Gang, which her father, Lord Cai, leads. The Scarlet Gang is engaged in a feud with the White Flower Gang, led by Lord Montagov. Juliette had a romantic relationship with Lord Montagov’s son, Roma, before she left for the United States. However, the two had a falling out after the White Flower Gang bombed the servants’ quarters at the Scarlet Gang’s headquarters, where Juliette and her family lived. In retaliation, the Scarlet Gang murdered Lady Montagova, Lord Montagova’s wife and Roma’s mother. After that, members of the Scarlet Gang and White Flower Gang often try to kill one another, and Juliette considers Roma her enemy.
Shortly after Juliette returns to Shanghai, people begin falling to the ground and tearing out their own throats for mysterious reasons. Rumors circulate that there is a monster haunting Shanghai. Roma comes to see Juliette to ask if she or the Scarlet Gang knows any more information about the monster and the so-called plague of “madness.” Juliette sends Roma away without speaking to him at length. That night, Juliette talks with a British merchant named Walter, who tries to convince her and the Scarlet Gang to buy lernicrom, a powerful new opiate. Juliette says the Scarlet Gang isn’t interested.
Meanwhile, Lord Cai is convinced that the Communist Party is behind both the monster and the madness and believes the Communists are using the monster to gain power. Juliette decides to investigate the matter with her cousins, Rosalind and Kathleen.
Lord Montagov assigns Roma to investigate the madness-inducing contagion and the monster. With the help of fellow gang members Benedikt and Marshall, Roma investigates. They find insects at sites where people have fallen ill and take those insects and corpses to a laboratory run by the White Flower Gang. There, a scientist named Lourens examines the insects and says they seem to be spreading the disease by infesting people’s hair like lice before burrowing and attaching themselves to people’s brains. Around that same time, Rosalind sees the monster. When she sees it, thousands of insects emerge, suggesting that the insects and the monster are related.
During their investigations, both Roma and Juliette hear rumors that Zhang Gutai, the Secretary General of the Communist Party, is behind the contagion. There are also rumors that someone known as the Larkspur has created a vaccine for the contagion of madness.
Juliette goes to Zhang Gutai’s office at a newspaper to investigate. While there, she’s surprised to find Roma, who is also there to investigate Zhang Gutai. Neither of them finds the information they’re looking for.
Not long after, Juliette and Roma meet again at a masquerade party. Juliette was invited to the party by Walter’s son, Paul, who is not only romantically interested in Juliette but is also trying to convince Juliette to buy lernicrom. Juliette spurns Paul’s business and romantic advances.
At the party, while Juliette is dancing with Roma, Tyler—Juliette’s cousin and main rival for power within the Scarlet Gang—pulls a gun on Roma because he, as a member of the White Flower Gang, is trespassing on Scarlet Gang territory. Roma’s fellow gang members, Benedikt and Marshall, step out from the shadows holding guns. Before anyone shoots, though, people begin falling to the ground, clutching their throats, as they’ve been afflicted by the contagion of madness.
Roma and Juliette then flee the scene to avoid becoming afflicted with the contagion. When they stop running, Roma tells Juliette that both gangs would accomplish more in trying to stop the spread of the contagion if they worked together. After considering the matter, Juliette agrees to arrange a meeting between the two gangs.
At the meeting, though, the two gangs are reluctant to share information, and tensions rise. The gangs eventually call off the idea of cooperating. As they leave the meeting, Roma’s sister, Alisa, falls down, gripping her throat. Roma rushes her to the hospital, where doctors sedate her. Because there is no known cure for the madness, the doctors say they will try to keep her sedated until they find a cure.
Afterward, Roma approaches Juliette and says that they should continue working together in secret to investigate the contagion and the monster. Juliette eventually agrees, though she still considers Roma an enemy. The two investigate Zhang Gutai and hear rumors that a monster is doing his bidding. They go to Zhang Gutai’s apartment, where they meet his personal assistant, Qi Ren. At the apartment, they find a note linking the Larkspur to Zhang Gutai.
The next day, four men follow Juliette when she goes to meet Roma. Juliette kills three of the men. The fourth tells them, under duress, that the Larkspur has put a bounty on them. Juliette and Roma then break into the Larkspur’s office, where they’re told that no one knows who or where the Larkspur is. Roma and Juliette take a vial of the Larkspur’s supposed vaccine back to the lab where Lourens works. When Lourens examines the vaccine, he says that it’s made of lernicrom. Juliette immediately knows that Walter is the Larkspur’s supplier.
To find out more information, Juliette meets with Walter’s son, Paul. At his house, Juliette finds an invoice with the Larkspur’s name on it, along with the name Archibald Welch. Juliette and Roma track down Archibald at a bar. He tells them where the Larkspur’s laboratory is and that the Larkspur is making both a real vaccine and a fake vaccine and using the two to essentially decide who lives and who dies from the plague of madness.
As they’re talking, police raid the bar. Juliette and Roma sneak upstairs to an empty room. They begin to kiss, but Juliette remembers how Roma betrayed her by taking part in the White Flower Gang’s bombing of the Scarlet Gang four years ago. She then leaves. The next morning, Juliette finds Roma and tells him that she wants to know once and for all why he betrayed her and her family by taking part in the bombing. Roma explains that, four years ago, when his father found out Roma and Juliette were romantically involved, Lord Montagov told Roma that he must kill Juliette. Roma said he would rather take his own life, and his father didn’t seem to object. As a result, Roma felt forced to come up with another plan so that Lord Montagov wouldn’t kill Juliette. After hearing why Roma took part in the bombing, Juliette begins to consider forgiving him, and the two decide to keep working together.
They then go to the Larkspur’s laboratory. There, they find the Larkspur, but he is wearing a mask. He tells them that Zhang Gutai is the monster. Juliette and Roma are convinced that if they kill the monster, they will stop the plague of madness.
Roma and Juliette go to Zhang Gutai’s office at the newspaper. When they find him, Juliette kills him. To their surprise, though, the madness doesn’t stop, and people continue falling to the ground and tearing out their own throats.
Juliette and Roma reconsider the evidence they have. As they put the pieces together, they decide that Qi Ren, Zhang Gutai’s personal assistant, must be the monster. They return to Zhang Gutai’s apartment. Inside, they find evidence of a struggle. They then spot Paul on the floor. When Juliette approaches him, he injects her with a vaccine. He then confesses to being the Larkspur. He explains that he brought a contagion-spreading insect from England and set it loose on Qi Ren because he believed Qi Ren was Zhang Gutai. He wanted to target Zhang Gutai because he was afraid that the Communist Party was gaining more political power, which would limit his father’s ability to conduct business in Shanghai. Paul hoped that the insect would pass the plague of madness from one Communist to another. To his surprise, it turned Qi Ren into a monster that served as a breeding ground for the insects. When there was an abundance of insects, Qi Ren would turn into the monster. When he shed most of the insects, he turned back into a human. Paul then developed a vaccine to profit from the contagion and to save the people he wanted to save.
Just then, the monster stirs in the apartment and then flees. Juliette chases after it, afraid of the damage it will cause as it sheds contagion-spreading insects while running down the street. Roma heads toward the river, where he believes the monster is going.
Roma reaches the river, and the monster arrives soon after. Paul and Juliette then arrive too. The monster dives into the river, releasing a cascade of insects that fall onto Roma. Juliette moves to help him, but Paul attacks her. Juliette fights with Paul, and the two fall into the river. Underwater, Juliette shoots Paul, killing him. When she resurfaces, Qi Ren is on land. Juliette apologizes before she shoots him. After she shoots and kills him, Roma is freed from the insects.
Roma and Juliette then go to Alisa’s hospital room. She has woken up and seems to have recovered, but Tyler is there and holds her at gunpoint. Other members of the Scarlet Gang also hold Benedikt and Marshall at gunpoint. When Roma and Juliette arrive at the hospital, Tyler accuses Juliette of being a traitor for working with the White Flower Gang. Juliette claims she has been tricking Roma by working with him. Marshall attempts to escape and kills a White Flower Gang member. Tyler then shoots Marshall, wounding him badly. Juliette says they must kill Marshall, too, because he killed a Scarlet Gang member. She shoots him. The two gangs then disperse, while Juliette stays behind to take care of Marshall’s body.
It’s then revealed that Juliette has only pretended to kill Marshall. After the gang members leave, she takes him to a surgeon, who operates on him. Juliette brings Marshall to a Scarlet Gang safehouse.
The next day, Juliette brings food and water to Marshall at the safehouse. After Juliette leaves that safehouse, a messenger brings her a note that Kathleen has found in Paul’s briefcase. The note says, “In the event of my death, release them all.” Juliette hears people screaming in the distance.