It happened near Shake Shack on 125th Street and 5th Avenue just before 10:30 p.m. Saturday.
The man in his 30s was shot in the torso and neck. He was taken to Harlem Hospital where he was pronounced dead.
Police say they are looking for two men who fled the scene in a Toyota.
No arrests have been made and the investigation is ongoing.
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The circumstances surrounding the shooting are unknown.
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