The victims are 17-year-old Christopher Malcolm and 13-year-old Rohan "Sonny" Bennett.
Philadelphia police investigators believe Malcolm may have been targeted by the gunman and that Bennett was caught in the crossfire.
Philadelphia police spent hours at the home on Tuesday night, located on the 1300 block of Westbury Drive in the Overbrook Park neighborhood.
"We believe that the motive of the shooting is possibly drug related because we did find some narcotics inside of the property and there are also other drug connections regarding this particular property," explained Philadelphia Police Chief Inspector Scott Small.
Police say the teens were in the living room of their home around 7:30 p.m. when the gunman burst inside and opened fire.
Police say Bennett was shot several times in the chest, and was able to run to the basement before he collapsed and died. Malcolm was shot in the chest and head and was pronounced dead at the hospital just after 8:00 p.m.
"There were several adult males in the house at the time. They were transported to homicide as witnesses," said Chief Inspector Small.
Family and neighbors wept and held a prayer vigil as investigators searched for evidence.
Multiple .45 caliber casings were recovered inside the home. Police say a large amount of cash was found inside the home along with narcotics.
So far, police do not have a detailed description of the suspect.