Crews used chainsaws to gain access through the roof of the home on the 400 block of Concord Avenue in Chester around 1:20 a.m. Sunday.
The upper floors of the three-story home were burning when firefighters arrived.
PHOTOS: Resident rescued in 2-alarm Chester fire
The victim was rescued from a third-floor room, and was taken to Crozer-Chester Medical Center for treatment where he later died of his injuries.
The fire spread to two vacant homes before firefighters were able to get the upper hand.
There's no word yet on a cause.