The fire broke out just after 6 p.m. Monday in a home in the 100 block of Smokehouse Lane, near Reedy Creek Road.
It took less than 15 minutes for firefighters to extinguish the blaze.
"The house is a total loss," said Cary Fire Capt. Dennis Jacot. "It'll have to be a rebuild. I don't think there'll be anything salvageable."
Ahmed el Sayed is a friend of the family of six who lived in the home.
He told firefighters the family is on vacation in Myrtle Beach right now. The family called Sayed to check on reports that their house was ablaze.
"I told him what happened. He says, 'Well, what are we going to do.' Thank God anyway. Thank God nobody was here," said Sayed.
"It's devastating. It doesn't matter what day of the week it is, a fire's devastating for anybody," said Jacot. "Let alone for it to happen in the holiday season. That's supposed to be joyful."
Two firefighters suffered minor injuries.
Investigators are still searching for the cause of the fire.
The fire shut down Reedy Creek Road for hours.