Neighbors said the deceased are a 39-year-old woman and her 14-year-old son.
The 12-year-old daughter survived and was taken to the hospital in stable condition.
"She cared about those kids. She loved those kids," Vikki McGarvey said of her sister, Linda, who died in the fire.
The family gathered to leave candles, flowers and mementos of the mother and her son on the steps of their home just hours after the fire.
"We've got a big family and everybody is a mess," said McGarvey. "We've got to just pull through and keep it together."
A 911 call came in around 12:40 a.m. on Wednesday for a report of a fire and people trapped on the 2200 block of Pierce Street.
Firefighters were met with heavy smoke on the first floor of the two-story row home.
"I was just praying for the best," said neighbor Asha Downing, who described hearing breaking glass and neighbors screaming as the flames burned.
The fire spread to the home next door. Neighbors were evacuated.
The news shook neighbors, who say the mother was known for giving out lunches to neighborhood children during the summer.
"Firefighters executed an aggressive interior search and rescue and fire fighting effort," said Philadelphia Fire Department Commissioner Commissioner Adam Thiel. "They did rescue three occupants from the building."
Neighbors watched as first responders try to revive the mother and son.
"The son and the mother perished together right there on the ground. They both were getting worked on," said Audrey Hill Jones, who lives right next door. "This is horrible."
Neighbor Asha Downing just saw the woman just hours before the fire.
"She came over and was joking with my kids and playing with them. Two hours later, this was happening," Downing said.
The cause of the fire is under investigation.
October is National Fire Prevention Month.