Seven News have confirmed the major crime squad is investigating a man's movements immediately after the fire.

Detectives have received information from several people about the man and whether he becomes a primary suspect will be become clearer after he's been interviewed.

Anyone with information that might assist investigating officers is urged to contact Crime Stoppers on 1800 333 000.

Meanwhile, police have now confirmed a fourth resident has died following the fatal nursing home blaze at Quakers Hills.

The person died while undergoing treatment for their injuries in hospital.

It had previously been reported that three people died in the blaze and 32 others were taken to Sydney hospitals suffering various injuries.

Fifteen of them were admitted to the intensive care units at Royal North Shore and Concord Hospitals – five with severe burns.

None of the deceased has been formally identified at this stage.

Roof falls after fatal nursing home fire

The roof of a western Sydney nursing home has collapsed after a deadly blaze destroyed the building and killed three people.

The coroner has attended the scene but police are warning of a long investigation.

"There's still some places we don't have access to because it is far too dangerous," Acting

Police Commissioner Catherine Burn told reporters.

"It's still an extremely dangerous fire ground in there.

"Only 15 minutes ago parts of the roof had collapsed in."

Ms Burn confirmed 32 residents were in hospital, 14 of them in intensive care units.

NSW NURSING HOME FIRE: 3 DEAD

Three people have perished and up to four more are feared dead after one of the worst fires in decades ravaged a Sydney nursing home.

"It is a scene of total devastation," said NSW Fire Commissioner Greg Mullins.

Firefighters were confronted by their "worst nightmare" when they arrived at the inferno on Hambledon Road, Quakers Hill, shortly after 5am (AEDT) on Friday.

Flames were licking the roof after engulfing two rooms while thick, choking black smoke filled the building, blinding firefighters who had to crawl on the floor.

Gallery: Quakers Hill Nursing Home fire

"(They) could not see their hands in front of their faces," said Comm Mullins.

"Crews had to literally crawl on their hands and knees into every room in the complex, reach up under the beds, searching cupboards, anywhere where someone may have crawled away."

NSW Police Superintendent Robert Redfern said at least three people had died, and the toll was expected to rise.

"A process needs to be followed to identify these people," he told reporters.

"Our hearts and thoughts and prayers go out to families of those that have been killed and injured this morning."

Comm Mullins said many frail residents could not get "out of harms way" and the "roof was on fire above them", he added.

"This is a firefighter's worst nightmare," he said.

"This has been a very, very serious fire, a tragic scene - a lot of people injured. There have been some fatalities, there may be more...

"It's decades since we've seen a fire like this."

Within six minutes about 90 firefighters were on the scene, almost immediately backed up by 50 ambulance crews, more than a hundred police officers and dismayed neighbours.

"It is just horrific, absolutely horrific," one neighbour told AAP.

"Tremendously sad that this has happened to gentle elderly folk."

Dozens of disorientated people in their nightclothes were lying on beds or sitting in wheelchairs receiving treatment from paramedics outside the home.

The driveway became a makeshift triage centre, as did a nearby Anglican Church.

"There's also a few that have turned up looking for their family and unfortunately their family hasn't been here," said the church's office manager Melinda Champion.

An aerial image of some of the damage caused by the nursing home fire. Source: 7News

It's hoped they have been moved to other nursing homes or to hospitals.

Police have urged families of residents not to go to the scene, but call 1800 227 228.

"It's a terrible tragedy," said Opposition Leader Tony Abbott.

"This is just the sort of thing that I suppose just fills people with horror."

Homicide detectives and fire investigators were at the scene shortly after 10am (AEDT), with police warning the investigation would be a lengthy process.

Comm Mullins said the fire, which is being treated as suspicious, had broken out in two areas of the facility.

"There will be specialised scientific testing, burn patterns, etc, and they will determine the cause," he said.

NSW Minister for Ageing and Disability Services Andrew Constance said it was a "horrific day" for the state and the country.

He said the state government was working with the commonwealth and his federal counterpart Mark Butler to try and arrange temporary accommodation for those residents affected.

"The commonwealth, who administers the nursing homes, we'll be working closely with them this morning and throughout the course of the day to look at options as quickly as possible," he said.

"We will be ... making sure that we have placements available to people in light of the fact that this facility is not going to be available."

Gary Barnier, CEO of Domain Principal Group which owns the aged care facility, said he had met with some of the resident and their families.

"I can't imagine what it was like for them ... they seem to be in as good a spirits as could be under the circumstances," he said.

"I was just making sure they got the proper attention."

Staff were being offered counselling and additional assistance, he added.

Emergency crews attend to evacuees of the Quakers Hill Nursing Home fire. Source: 7News

TOUGH JOB FOR DOCTORS TO SAVE FIRE VICTIMS

Specialist doctors treating elderly victims of a Sydney nursing home fire face a tough battle helping them overcome burns and smoke inhalation.

Experts say aged patients injured in fires do not tend to cope well.

For those with dementia, a terrifying event like a fire can worsen their general confusion.

Some of the most severely injured survivors from Friday's Quakers Hill blaze are being treated by specialists at two major hospitals - Concord and Royal North Shore.

Professor Peter Maitz, of the burns injury and reconstructive surgery unit at Sydney Medical School, Concord Hospital, says burns are especially tricky to treat in elderly patients.

Doctors cannot rush them into the operating theatre as they would a young person because symptoms of smoke inhalation always have to be treated first.

Any pre-existing medical conditions, such as emphysema, also need to be taken into account.

"We know it's going to be very difficult," said Prof Maitz as he prepared to treat two of the most seriously burned patients from Friday's fire.

Smoke inhalation increases an elderly burns patient's chances of dying by 40 per cent.

Patients are usually sedated and hooked up to ventilators pumping pure oxygen into their lungs to repair damage caused by soot and smoke particles.

Doctors then wait three to five days to assess any burns.

Prof Maitz said elderly people struggled with burns because chemical compounds known as cytokines, which are released when skin burns, affect major organs.

While young healthy people's bodies can fight the cytokines, elderly patients are not usually as strong.

"So we see a 20-year-old surviving 90 per cent burns but we don't see a 90-year-old surviving 20 per cent burns," Prof Maitz said.

For patients with dementia, being in a fire can be extremely disorienting.

"It would be bewildering, frightening and people may regress in their behaviour," said Professor Henry Brodaty, of the Dementia Collaborative Research Centre at the University of NSW.

Prof Brodaty said being taken to another nursing home or hospital with unfamiliar faces and routines would add to their confusion.

But having plenty of support from family and other familiar faces would help dementia patients cope with new surroundings.