A security guard is dead and another man is fighting for his life after a drive-by shooting outside a popular Melbourne nightclub, police said on Sunday.

The shooting, which happened at about 3.20am, came amid a spate of gun violence in Australia's second-largest city.

Police said four men - three security guards and a patron waiting to get in - were shot outside the Love Machine club in the trendy inner-city suburb of Prahran.

"It would appear that shots have been discharged from a car in this area into a crowd that was standing outside the nightclub," Victoria Police Inspector Andrew Stamper told reporters.

"This is just a horrendous act. It's a busy nightclub, one of the main nightclubs in Melbourne in one of the main entertainment precincts in Melbourne."

The 37-year-old security guard was taken to hospital but died soon after.