Investigators were able to rescued the man after responding to the fire Tuesday morning on Grey Fox Court off of Southwest Cary Parkway.
Wednesday morning they said 29-year-old Ryan Crosby died at UNC Jaycee's Burn Center.
Another who was at the home is being treated for injuries.
When fire crews arrived on scene they saw heavy flames and smoke coming out of a window on the second floor of the house.
The cause of the fire remains under investigation, however, Cary fire officials said they believe it started in the second-story bedroom that Crosby was rescued from.
"Our hearts are heavy today following yesterday's tragic event. First responders followed protocols and did everything they could to prevent loss of life and minimize property destruction. I want to thank everyone who supported this incident for their tireless effort and dedication," Cary Fire Chief Mike Cooper said.