The fire started in the single-story building on Thong Nhat Street at around 2 a.m. with the two children sleeping on the mezzanine.
They had been at home on their own since their parents, both vendors, had left for the Binh Dien Wholesale Market which is nearly 30 km away in District 8.
The couple rents the house to retail fresh seafood.
Neighbors detected the fire and rushed to put it out with portable extinguishers, but it was in vain.
Two firetrucks and 15 officers arrived and put the fire off within 10 minutes.
But by the time they broke open the door to reach the children, they had died of asphyxiation.
Police said the house was locked from outside, and an electrical short circuit was the possible cause of the fire.