A woman and three dogs died after being unable to escape the blaze which took hold in the early hours of Wednesday morning.
Emergency crews rushed to the scene on Spring Road, Ettingshall, at 2.26am.
Two others in the house managed to get out, with one man treated for serious injuries – including burn injuries – before being taken to Queen Elizabeth Hospital in Birmingham.
A second man was treated for the effects of smoke inhalation before being taken to New Cross Hospital for further assessment.
Both men had escaped the property before crews arrived, with one of them jumping from the first floor window to safety.
Marion Brown, 35, who lives next door with her family husband and three children, had to evacuate her home.
She said: "I know them, but I don't know what has happened fully.
"When I heard the first noise it was around 2:15am, because my daughter woke up. I thought maybe it was the neighbours dog or something at first.
"But then I heard noises of people struggling, and I thought 'that is quite loud' because at that time everything is quiet.
"Before I could get my thoughts together I heard a loud noise, which sounded like a mirror breaking.
"I came down to look and I could just see smoke. I ran out with my kids and I could see the neighbour on the roof. I rang 999 and I was screaming 'there's a fire, Ettingshall, Spring Road'.
"They sent three fire engines, the fire and everything happening was a lot to see. I know them, I say hello, how are you, if I see them.
"They are very nice people. We evacuated and stayed next door while it happened, I had my 6-month-old in my arms."
Six firefighters wearing breathing apparatus extinguished the fire, using hose reel jets.
A spokesman for West Midlands Fire Service said: "Very sadly, one woman and three dogs were unable to escape the fire and were confirmed to have died at the scene. Our thoughts are with everyone affected by this incident.
"Investigations into the cause of the fire are continuing."
Three fire engines and a brigade response vehicle responded, crewed by firefighters from Bilston, Wolverhampton and Dudley fire stations.
The first appliance arrived three minutes after being mobilised, fire chiefs said.
Meanwhile, two ambulances, two paramedic officers, a MERIT trauma doctor and a HART paramedic were sent to the scene.
A spokesman for West Midlands Ambulance Service added: "A man was treated for serious injuries, including burn injuries, before being taken to Queen Elizabeth Hospital, Birmingham.
"A second man was treated for the effects of smoke inhalation before being taken to New Cross Hospital for further assessment."
The owner of L&D'S Diner, Dean Isherwood, didn't know those involved but described it as a "real shame".
He said: "I came to work this morning and that was the first I heard of it, at 5am, and I only live down the road.
"I didn't know them, an elderly couple lived there before and I thought it was them originally, I didn't know they had moved out.
"It is a shame really, she is only a young girl, it shouldn't have happened."