Elizabeth Perez initially escaped the blaze with other relatives after it broke out at 4am on Friday in the city's Fairhill neighbourhood.
But after realising her toddler, two-year-old Nathaniel, was missing, she ran back inside to try to save him.
Ms Perez, who was eight months pregnant, was found holding the child near a second-floor bedroom doorway.
"It's not a pretty sight," Philadelphia Fire Commissioner Derrick Sawyer told NBC Philadelphia, "her holding her child in her arms trying to get back out."
The fire's cause is under investigation, but officials said the home had no working smoke detectors.
One of five heaters found throughout the house may have ignited a blanket, say fire investigators.
Two adults and four children were taken to a hospital, where they were in a stable condition.
Ms Perez had been due to deliver a baby girl, to be named Secret, on Valentine's Day, reports the Philadelphia Inquirer.
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