It happened around 4 p.m. on the 2000 block of South Beechwood Street.
Police say four officers arrived to find the 36-year-old male suspect actively stabbing his 72-year-old aunt inside the residence.
Officers then Tased the man but police said it had no effect.
"The male was brandishing a hunting knife, a large hunting knife. They ordered the male to drop the knife. (He) disregarded their orders at which point the officers drew their Tasers and attempted to tase his at least two times," said Philadelphia Police Sgt. Eric Gripp.
Investigators say the man was shot at least one time after he declined to put down the weapon and lunged at officers.
"We heard three pops, three gunshots," said Michael Bucci who was working nearby. "It's unsettling."
The unidentified suspect and his aunt were both transported to an area hospital where they later died.
There was no immediate word on what sparked the stabbing.
"The senseless violence in the city is affecting everyone... We will not rest until all responsible are brought to justice," said Commissioner Danielle Outlaw in a tweet following Tuesday's violence, which also involved a 12-year-old girl being shot.
Police say the officers involved have been put on administrative duty pending the outcome of the investigation.
The senseless violence in the city is affecting everyone. Within minutes and on opposite sides of the city, 2 women and 1 young girl's lives were completely changed by violence. Their ages range from 12 to 72. The 12 y/o child is in stable condition after she was shot...— Danielle M. Outlaw (@PPDCommish) February 15, 2022