It happened just after 1 a.m. on the 5600 block of Warrington Avenue.
Police and medics responding to reports of gunshots found a 24-year-old man lying on the living room floor. He had been shot in the face.
The victim was pronounced dead at the scene.
Police also located a man inside the home who was in a wheelchair.
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Police believe this man, who lives in the home, was the shooter. He was taken into custody and is cooperating with authorities, police say.
A weapon was also recovered at the scene.
Small said it appears one shot was fired.
"The 24-year-old...we believe does not live at this location, however, he is an acquaintance of the shooter," Philadelphia Chief Inspector Scott Small said.
Small said they do not know the motive or what led to the shooting.
There was no one else at home at the time.
"We do have neighbors who heard at least one gunshot; they are being interviewed by homicide detectives," Small said.
Police say the shooting victim's last known address is outside the city, but an identity has not been released.