The shooting happened outside the Love Machine nightclub in Prahran, at around 3.20am local time (6.20pm GMT).
Officers confirmed four people were rushed to hospital.
A 28-year-old man and another man whose age was not immediately available were said to be in a critical condition.
Officials also confirmed a 50-year-old man and a 29-year-old man wounded in the shooting.
They are said to have non-life-threatening injuries.
It is understood one of those injured was a security guard.
A Victoria Police spokesman said: “The exact circumstances are still being established.”
Police didn’t offer further information about the victims.
“The exact circumstances are still being established”
Victoria Police spokesman
According to reports, the gunman was using a stolen Porsche.
A witness on social media said they are “in shock” after seeing a shooting “right in front of us…while we were standing across the road”.
“Please if anyone is out at clubs please go home now. We are all in shock but we are all okay.”
Malvern Road was closed in both directions between Chapel Street and Surrey Road.