Police believe a man with gunshot wounds who died on a suburban driveway was a home invader who was shot during a struggle.
A search is now underway for several others wanted over the violence in what's believed to be targeted attack at a residential address in Donnybrook, about 50 kilometres north of Melbourne's CBD.
Investigators believe three to five offenders armed with at least one handgun and a machete forced their way into the Middlemount Street home at about 4.20am on Sunday.
At least one of the men assaulted a 27-year-old female resident with the knife before a male resident confronted the group, Detective Inspector Graham Banks said.
"There's been some sort of struggle and a firearm has been claimed off one of the offenders who has come to the house," Insp Banks told reporters.
"Shortly after that several shots have taken place."
The dead man was found in the driveway by police and a window at the home appeared to have been smashed.
He is believed to have been one of the armed offenders but has not been formally identified, police said in a statement.
After the incident, a Clifton Hill man, 22, with gunshot wounds presented to the Northern Hospital in Epping before being transported to the Royal Melbourne Hospital for surgery.
Officers are still working to establish whether he was involved but say he's a person of interest due to the time he turned up at hospital.
The injured female resident fled to an address in Doreen, about 20 kilometres away from the home, and has since gone to hospital for medical treatment.
The male resident, 28, is assisting with the investigation.
Police said a firearm was found at Kumalie Drive in Doreen and were working to confirm if it was used in the home invasion.
Insp Banks said it was still too early to confirm a motive for the incident and officers were focused on identifying all the parties involved.
"It's quite a shocking incident but as I say, we do not believe it is related to anything beyond that household," he said.
He also confirmed one of the Donnybrook residents was known to police.
Anyone who may have seen anything suspicious related to the incident at Donnybrook, the Northern Hospital or Doreen has been asked to come forward.