After receiving a message from his on-again off-again love interest Fujiko Mine, master thief Lupin the Third has just arrived in the ancient city of Canghai along with his partners Jigen and Goemon. However, when they arrive at the meeting point, a mafia boss named Kouring shows up, demanding Lupin's cooperation in exchange for Fujiko's life. Of course, Lupin is having none of that, and tries to rescue Fujiko himself, but winds up cursed by an ancient black art, which will kill him in three days. Ancient documents that Fujiko found show that the Cang dynasty treasure she's looking for may also hold the key to curing Lupin's curse. But with only three days, will they be able to find the treasure and save Lupin's life?

Lupin Sansei: Lupin ni wa Shi o, Zenigata ni wa Koi o ("Lupin the Third: Lupin is Dead, Zenigata is in Love") is the third and final PS2 game based on the popular Lupin the Third anime franchise. There is less of a focus on stealth compared to the previous titles, but it is still possible to use disguises to sneak past and glean information from enemies. The player also controls Jigen, Goemon, and Fujiko at certain points, each with their own unique game style. The player also takes control of Inspector Zenigata in some chapters, a first for the series. At certain points, Lupin and Zenigata must actually work together to escape or defeat enemies.

Taking a departure from previous Lupin III games, the latest PS2 offering features an engaging 3D action-adventure that's peppered with quick one-button-press interaction challenges as well as more involved gaming sequences that last a few minutes each. The games are linked together by cut scenes between Lupin and crew as well as 3D exploration and discovery sessions. In an early level of the game, Lupin beats up a member of the police corps and takes his uniform. He may then skulk around the grounds partially disguised while collecting clues and hints. However, since Lupin's face and manner is so distinctive, the other cops are sharp enough to discern him from one of their own if they get close enough to examine him. Once the jig is up, Lupin will have to do some running and Dual Shock wagging to knock cops off his limber frame.