The victim was carried out of the house in Dickens Road in the Low Hill area of Wolverhampton by firefighters but despite efforts to save him he died at the scene.
Fire crews arrived within three minutes of being called to the blaze, which was on the second floor of a three-storey building which had been sub-divided into bedsits and started at around 1am.
It is not yet known what caused the fire but West Midlands Police said it was not being treated as suspicious.
"Thirteen residents managed to get themselves out before we arrived," a West Midlands Fire Service spokesman said.
"Firefighters wearing breathing apparatus recovered one man from the building but, very sadly, he was confirmed by the ambulance service to have died."
Two fire engines and a Brigade Response Vehicle, crewed by 13 firefighters from Wolverhampton and Fallings Park initially attended, before being joined by crews from Willenhall, Bilston and Dudley.
Neighbours were left stunned by the blaze and sudden loss of life as the road remained cordoned off on Thursday morning with the smell of burning still lingering in the air.
Justyna Feliks said she was woken around 1.30am by the sound of sirens and looked outside to see multiple fire engines and crew on the road.
She said: "I looked and saw a lot of fire engines and smoke on the street, as well as a lot of people running around on the street.
"I've just found out that someone has died and it's horrible news to hear about that as these people are neighbours and while I didn't know them personally, you'd see them walking around."
Another neighbour, who didn't want to be named, said it was sad to hear about a life lost.
She said: "I was woken by a racket outside and tried to sleep through it, so I didn't know until this morning it was a house fire and that someone had died.
"They're all young people who live in that house as I see them come and go and it's really sad to hear one them has died."
Fire investigators were continuing to examine the scene throughout Thursday morning.
West Midlands Ambulance Service said medics were called at 1.15am, with two paramedic officers and the Trust’s Hazardous Area Response Team attending the scene.
A spokesman said: “On arrival crews discovered one patient, a man, who had been rescued from the property by the fire service.
“Sadly, it quickly became apparent nothing could be done to save him and he was confirmed dead at the scene.”