The fire was reported around 4:45 a.m. at a home in the 5200 block of Chancellor Street. No working smoke detectors were found in the home.
"We don't know the cause yet, but we do know with early warning you can get out of your house," said Philadelphia Fire Commissioner Lloyd Ayers.
2-year-old Jayden McClendon 4-year-old Cincere McClendon were rushed to the hospital, but they couldn't be saved. Medics previously said the children had burns to "100 percent" of their bodies.
Jayden's mother, 23-year-old Rishya Jenkins, was pronounced dead at the scene.
"She loved them, she would do anything for them. That's why she was still in there with her boys, trying to get her boys out of there," said cousin Nikia Peterson.
The 68-year-old paternal grandfather of the boys, Seneca "Chuck" McClendon, also died at the hospital. All four were trapped on the second floor when the fire broke out.
The father of the two boys arrived home from a double shift at work to find his home engulfed in flames. Friends say he has already lost two brothers and now must cope with the losing his father, his girlfriend, and children. ?
"They had to restrain him because he was trying to get in to save his family. I admired his efforts, I watched him grow up, but he could not get in because the flames were really bad at that point," said neighbor Esther Woods.
The fire was placed under control in 38 minutes. Fire Commissioner Ayers says there have now been 14 fire deaths in the city this year.
"We're asking the whole city to lift us up in prayer," said Ayers.
The Red Cross will be out on Monday afternoon to hand out fire prevention information and smoke detector batteries. Ayers also urged anyone who needs a smoke detector in Philadelphia to call 311.