A deadly arson attack that claimed the life of a young woman who was house-sitting for her brother while he went on their honeymoon may have been a tragedy of mistaken identity.

The 27-year-old man was trapped in a three-storey townhouse on Dover Street in Truganina, in Melbourne's west, when a fire broke out about 2.30am on Thursday.

A Hoppers Cross woman called emergency services to raise the alarm but she did not survive.

Victoria Police Inspector Chris Murray said two people were seen getting out of a car and pouring accelerant into the house before it was engulfed in flames and her death was being treated as a homicide.

"This man was completely innocent and did not deserve to die," he told reporters on Thursday.

“We don’t have the history of this person, we don’t have the history of this family.

"My initial assessment is that these offenders were targeting the wrong address and it's just a tragedy."

Murray described the woman as "the kind of girl who doesn't leave home very much".

"She was subjected to the most shocking, despicable behavior one could imagine," he said.

Sahil Arora, a resident who lives next door to the destroyed townhouse, woke up to the sound of shattering glass.

He and his wife evacuated their home and watched as a neighbor's house caught fire and the streets filled with heat and smoke.

Arora didn't know the lady at the door but had met the couple who lived next door many times.

"I am deeply saddened and sincerely hope there is no one inside," he told AAP.

He said he now felt "a little scared" and warned such a tragedy could happen to anyone.

"Whether they were intentionally destroying these homes or just creating a scare tactic, now they are facing charges of homicide or murder," Murray said.

"It's nothing short of a tragedy that an innocent young lady lost her life."

Police believe the two men who fled are men but have no other information, including whether they were injured in the attack.

"If they go to hospital or see a doctor, if anyone sees someone coming home with burns, we want to hear that again," Murray added.

A pet golden retriever is also believed to have died in the fire, police said.

Police plan to increase patrols in the area but have not issued a safety alert to the wider community.

The arson and explosives detective slammed criminals' fascination with fire as a way to retaliate or settle disputes, particularly attacks linked to the illegal tobacco wars between crime syndicates.

He ruled out any link between the Truganina fire and the ongoing crime war but said money was often a factor behind attacks.

"I know the types of people who do these (acts), they do it for a few hundred dollars thinking they're going to burn something," he said.

"It's just a matter of time before they start using arson as a crime."

Investigators are searching the area for CCTV and are urging anyone with additional footage to come forward immediately.