A blaze broke out at a panel shop on Bunnett Street in Sunshine North at 4am on Friday.
It then spread to the factory behind where the two people were sleeping.
Both died at the scene and have not yet been formally identified.
The single-level factory was fully engulfed by the time firefighters arrived and it took three hours for about 50 firefighters to get the blaze under control, a Fire Rescue Victoria spokeswoman said.
"The incident has been deemed suspicious and Victoria Police has established a crime scene," she said.
Detectives believe the fire was a targeted attack and the two people killed were not connected to the panel shop, Victoria Police said.
The fire is also not believed to be linked to any other recent fires or Operation Lunar, a probe into Victoria's illicit tobacco trade and a violent conflict between crime groups over profits.
The cause of the fire remains under investigation and officers have urged anyone with information about the blaze to come forward.
Crews also responded to a factory fire at Malcolm Place at Campbellfield in Melbourne's north on Friday morning.
11°C