The pedestrians were hit while crossing Bruckner Boulevard at East 138th Street at around 4:30 a.m.
The victims, one a 20-year-old man from Harlem, were pronounced dead at the scene. The second victim has not been identified.
Witnesses say they saw the two men stumbling in the street shortly before they were hit.
The vehicle that struck the victims left the scene.
There were no immediate witnesses to the crash, and police did not have a description of the vehicle.
Some who live in the area reported that the men may have lived underneath the bridge in a makeshift camp.
The investigation is ongoing.