Police believe multiple people were shot during the incident and say a 28-year-old man and another who is yet to be identified are in critical conditions.
Police said the incident occurred on Sunday morning at around 3:20 a.m. local time (1720 UTC Saturday) at the Love Machine club in the southeastern suburb of Prahran.
A 26-year-old man took himself to hospital on Sunday afternoon with injuries stemming from the shooting, but they were not life threatening.
Those with video footage of the incident or information that could assist police with their investigation are urged to come forward and call Crime Stoppers on 1800 333 000 or make a confidential report online.
One person lost his life while two others were critically injured.
A security guard is dead and three others were seriously injured after a gunman fired indiscriminately into a group of people outside this busy Melbourne nightclub Sunday night.
It is learnt that a security guard was shot in the face during the attack, which according to the police appears to be a drive-by shooting case.
A stolen black Porsche Cayenne used in the shooting was later found burnt out in Wollert in the city's north.
Steve Yousif, who describes himself as a Love Machine host, posted on Facebook that "the love machine family lost a lovely soul today".
"Obviously they're gunshot wounds from fairly close proximity, so horrific injuries", he said.
That vehicle was later found burnt out in the suburb of Wollert. Neighboring New Zealand has adopted legislation to ban semi-automatic firearms and assault rifles after its worst peacetime shooting in March, which killed 50 worshippers in two mosques in the city of Christchurch.