A police spokeswoman said the woman, in her 70s, noticed the fire and ran outside to seek help from neighbours before emergency services were called about 7.50pm on Thursday.
Firefighters rushed to the unit on Chesterville Road at Highett, about 17 kilometres south-east of the CBD, and extinguished the blaze but found the man dead inside.
The woman was taken to hospital with minor injuries.
The area has been declared a crime scene as part of normal protocol surrounding a fatal fire and the arson squad will attend in the morning.
The police spokeswoman said it was too early to say what may have caused the fire.