Police responded to a home along the 1500 block of North Gratz Street around 9:30 p.m. Sunday.
They arrived to find a 49-year-old man with multiple gunshot wounds in the vestibule of the home.
Officers say the shooting happened upstairs, but the man made it downstairs.
He died at the hospital.
"We're still trying to determine exactly whether or not this was a case of self-defense or whether the woman acted in a matter that was the aggressor. We're still investigating that at this time," said Inspector D.F. Pace of the Philadelphia Police Department.
The woman is in custody and was being interviewed by homicide detectives overnight.