Fire Rescue Victoria (FRV) received multiple Triple-0 calls for a house on fire in Carinya Boulevard, Burnside, not long after 12am on Tuesday.
Firefighters found the rear of the two-storey brick residence well alight and that the fire had spread between floors and entered the roof space.
It took 30 firefighters and 10 appliances more than an hour to bring the fire under control.
The three residents safely evacuated the fire.
Damage to the house and contents has been severe and the residents will be sourcing alternative accommodation.
Investigators will be attending in the morning to determine the cause of the fire.
Firefighters will remain on scene for some time to continue to extinguish and undertake fire duties.