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The Killer’s Game follows veteran assassin Joe Flood (Bautista), who is diagnosed with a life-threatening illness and authorizes a kill on himself to avoid the pain that is destined to follow. After ordering the kill, he finds out that he was misdiagnosed and must then fend off the army of former colleagues trying to kill him.

Soulmates Eric Draven (Skarsgård) and Shelly Webster (FKA twigs) are brutally murdered when the demons of her dark past catch up with them. Given the chance to save his true love by sacrificing himself, Eric sets out to seek merciless revenge on their killers, traversing the worlds of the living and the dead to put the wrong things right.

The sequel picks up with Big Nick tracking down bad guys on the streets of Europe and getting closer to capturing Donnie (Jackson). Donnie, meanwhile, has become caught up in the dangerous world of diamond thieves and the Panther mafia, as a heist on the world's largest diamond exchange is being planned.