Emergency services responded to reports a man was shot on Mahoney's Road in Reservoir, in Melbourne's north, at about 11:50pm on Tuesday night.
The man is yet to be formally identified and a crime scene has been established, with Homicide Squad detectives on the scene.
"A short time after the shooting, a vehicle was located burnt out nearby in Thomastown on Robinvale Avenue with the offenders fleeing the scene of the fire in a white coloured vehicle," Victoria Police said in a statement.
Investigators are working to determine if the vehicle fire was linked to the fatal shooting.
As of early Wednesday morning, no arrests had been made and the investigation into the circumstances surrounding the incident was ongoing.
It is the latest in a string of recent public shootings in Melbourne.
On October 15, a man was shot dead in a home in Wollert, in Melbourne's north, in what police said was linked to organised crime.
The victim, a 42-year-old Wollert man, was shot multiple times and found dead inside a family home.
On September 6, Daniel Hussein, 22, was killed during gunfire in Thomastown after what police said was an altercation in a car park.
On August 16, alleged gangland boss Fadi Haddara was left critically injured after being shot outside his Altona North home.
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