In 1938 Shanghai, amidst the chaos of the Japanese occupation, Glendon Wasey (Sean Penn), an American traveling salesman fluent in Chinese, finds himself drawn into an urgent mission. He is approached by British Salvation Army missionaries, Mr. Burns (Michael Aldridge) and Gloria Tatlock (Madonna), who seek his help in locating Wu Ch'En She, the father of a wounded soldier. Initially, Gloria is put off by Glendon's careless demeanor, reckless language, and his struggles with alcohol, yet she recognizes his understanding of the local culture.
Their search quickly leads to trouble when a mob of local men confronts them. Justin Kronk (Philip Sayer), a European gentleman, pursues them but they manage to escape in rickshaws. Kronk claims that he can locate Wu Ch'En She, who is rumored to be in debt to various gamblers. For a fee, he introduces them to Ho Chong (Victor Wong), an insurance agent who has insights into Wu Ch'En She's whereabouts. However, Ho Chong misleads them, leading them onto a fishing vessel where they are trapped in a cargo hold filled with live fish—a harrowing message from the ominous Red Society.
While recuperating at the communal baths, Glendon is informed by Kronk that Wu Ch'En She has no sons, and that the fish was a signal. Confronted by Gloria, she reveals her true motivation: she needs morphine for the soldiers and seeks to reclaim opium stolen by Wu Ch'En She from the opium king, Walter Faraday. Glendon, aware of Faraday’s murder at the hands of local criminals, is reluctant to get embroiled in the situation; but Gloria’s mention of Mr. Burns holding his supply of glow-in-the-dark neckties pushes him towards complicity.
Mr. Burns, feeling responsible for Glendon's predicament, gives him a one-way ticket to Los Angeles along with some cash for new clothes. Gloria invites him to a duck dinner, where they are soon joined by journalist Willie Tuttle (Richard Griffiths), an expert on Faraday’s dealings. Willie shares a story from the night of Faraday's demise, detailing how he witnessed five crates of premium opium. Despite initial hesitation, and under pressure from Gloria, Glendon agrees to meet Faraday's concubine, China Doll.
After spending the night with China Doll, Glendon returns to his hotel room to face a disappointed Gloria, who pressures him for information. During a particularly tense moment, Gloria cleans his wounds, revealing her concern. As he refuses to see China Doll again, Gloria seduces him, leading to feelings of guilt that prompt her to set him free from their arrangement.
In a troubling twist, it's revealed that China Doll connected Wu Ch'En She with a tycoon, Joe Go, who has switched the opium for bricks and a small ball of opium. After learning valuable clues about reuniting with Wu Ch'En She, complications ensue with the reappearance of Kronk, who continues to demand payment for information. Amidst escalating chaos, Gloria and Glendon find themselves trapped by gangsters—but not before uncovering that corrupt officer Mei Gan (Kay Tong Lim) has his own interests in Faraday's opium.
In a climactic confrontation, Gloria and Glendon manage to reclaim their jewels, only to discover Faraday's deceit—he reveals the jewels are fakes and makes nefarious plans to ensure Glendon's involvement. After a series of narrow escapes, they find themselves reunited with Mr. Burns, who frees them from Faraday’s influence. The final moments see Glendon and Gloria standing united at the docks, as they thwart Faraday's schemes and uncover hidden opium among Glendon's ties. As the ship sails away, their future together begins to take shape, hinting at the adventure ahead.
