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Max Payne (James McCaffrey) is a former NYPD officer-turned-DEA agent whose wife Michelle (Haviland Morris) and newborn daughter Rose were murdered by armed junkies that were high on a new designer drug called Valkyr. In 2001, three years after their deaths, Max works undercover within the Punchinello Mafia family, who control the trafficking of Valkyr. His DEA colleague, B.B. (Adam Grupper), arranges a meeting between Max and his friend and former colleague, Alex Balder (Chris Phillips), in a subway station. While waiting for Alex, Max accidentally gets in a shootout with mobsters working for Punchinello underboss Jack Lupino (Jeff Gurner), who are staging a bank robbery through an abandoned part of the subway. When Alex arrives, he is killed by an unseen assassin, who frames Max for the murder.

Hunted by both the police and his former mob associates, who now know he is a cop, Max searches for Vinnie Gognitti (Joe Dallo), Lupino's right-hand man, in the hopes that he will lead him to Lupino. Along the way, he breaks up a Valkyr drug deal and discovers that Russian mobster Vladimir Lem (Dominic Hawksley) has started a war with the Punchinello family. After catching Gognitti, Max interrogates him and learns Lupino is at his nightclub, the RagnaRock. Max kills Lupino before running into Mona Sax (Julia Murney), a contract assassin and the sister-in-law of Don Angelo Punchinello (Joe Ragno). Mona, seeking revenge against Punchinello for abusing her sister and not wanting Max to get in her way, gives him a drink laced with Valkyr. While experiencing a nightmare of the night his family was killed, Max is found by mobsters and taken away to be tortured, but manages to escape.