Police have confirmed three people remain unaccounted for after the blaze erupted on Albermarle St in Newtown.
Fire crews were called to the scene at about 1am and the fire has now been extinguished.
Large bangs from the blaze were heard streets away, but police would not speculate on the cause.
Firefighters have told 9News the building is unsafe to enter, with hotspots and reignition continuing this morning.
Engineers are traveling to the scene to determine how best to proceed with investigating the residence.
Police said eight residents were able to exit the building, with three people taken to hospital.
They include a man in his 80s who is in a critical condition.
Two of the residents had to “exit from the second storey”, police said, due to the intensity of the fire.
Police are making inquiries to account for all residents of the building, and are yet to speak to the building’s owner.
A number of neighboring homes were also evacuated with no other reports of injuries.
The cause of the fire remains unknown.