It is the second-largest venue and show court for the Australian Open, the first Grand Slam professional tennis tournament held each calendar year.

[1] The venue is able to hold a maximum spectator capacity of 11,000 for events such as music concerts where general floor seating or standing room is available.

Meanwhile, temporarily throughout the 2006 Commonwealth Games, the Hisense Arena reverted to being called "Multi Purpose Venue" for the duration of the sporting event.

[9] In August 2018, Tennis Australia announced it had bought the naming rights and had elected to call it Melbourne Arena, saying it preferred a non-commercial title "iconic with the city".

The Phoenix, who made their debut in the 2019–20 NBL season, share their home with John Cain Arena and the State Basketball Centre in Wantirna South.

This broke the previous basketball attendance record of 9,308 set in 2008 in a local derby game between the South Dragons and Melbourne Tigers.

On 4 February 2023, John Cain Arena hosted a WNBL game between the Southside Flyers and the Sydney Flames following increased interest in the match due to the participation of Hall of Fame player Lauren Jackson.

Its name was changed to Multi-Purpose Venue with all Vodafone-related signage covered over with black shrouds because Telstra, a competitor of Vodafone, was a major sponsor of the games.

On 14 and 15 June 2013, the venue played host to an ice hockey exhibition series between teams representing the United States and Canada.

On 18 September 2018, Taiwanese vocal pop band Mayday held a concert for Life Tour supporting their album History of Tomorrow.

In November 2022, a stampede occurred outside the venue prior to a concert for American singer Steve Lacy, with poor organization by stadium management being blamed for it.

The concert was originally fixtured to be held at The Forum Theatre in Melbourne's central business district, but was upgraded due to high demand.