Police were called to Chapel Street in Prahran at around 1.30am following reports a man had been stabbed during an altercation.
The victim, aged 30, was taken to hospital, however he died shortly after.
It is understood an altercation began outside of Love Machine nightclub.
Police were told a group of men assaulted the victim and chased him down the street.
The man, from Mickleham, was then stabbed outside another venue on Chapel Street, police said.
A gun, or what could be an imitation firearm, was found in the “vicinity of the scene” and police have taken it away for forensic examination.
It is unclear if the gun is related to the stabbing.
A crime scene has been established and Chapel Street is closed between High Street and Greville Street
No arrests have been made and an investigation is now under way.
Police are now speaking to witnesses and are urging anyone who was in the area to come forward.
Anyone with information is urged to contact police or Crime Stoppers on 1800 333 000.
