Some might argue that all derbies are must-win matches but the importance of Saturday night's all-Melbourne clash is even greater than normal as a loss could be fatal to Victory and City's A-League championship hopes.
Both Victory and City will enter the derby at Etihad Stadium in poor form and knowing three points could be decisive in the race for a top-two finish.
Sydney FC's 2-1 win over Victory last week has effectively ended the battle for first place and the A-League premiership.
But with no team having won the grand final from outside the top two positions, Victory's coach Kevin Muscat and his City counterpart Michael Valkanis will be well aware of the significance of the fourth derby of the season in all competitions.
The two Melbourne clubs appear to pose the most danger to Sydney in the finals due to their impressive firepower up front but having to play two matches before potentially meeting the Sky Blues in the grand final could be too much of an ask.
City are the only side to have overcome Sydney this season, with Tim Cahill's header securing a 1-0 win in the FFA Cup Final in November, while Victory have led the Sky Blues twice in the A-League only to succumb in the second half on both occasions.
In particular, City desperately need to continue their derby dominance of 2016-17, with Valkanis' men having dropped to fourth after a loss at Newcastle Jets last week, while Brisbane Roar leapfrogged them with a win over Western Sydney Wanderers.
If City lose they will drop nine points behind second-placed Victory with nine matches remaining before the finals, while the gap to Roar could be as much as four points if Brisbane end Sydney's unbeaten run on Friday.
Bruno Fornaroli and Co. have the opportunity to get themselves out of a sticky situation during February as they face the other three members of the top four, but a second straight loss to Victory would be a dreadful way to start such a vital month.
City won two derbies in just over a week in October as they crushed Victory 4-1 in Round 2 and then eliminated their archrivals from the FFA Cup, but the Big V bounced back in December with a 2-1 win in the A-League.
After three straight losses, Victory have essentially dashed their hopes of lifting the Premier's Plate this term but with games against clubs currently in the bottom half of the table coming up after the derby, Muscat's side can reboot their campaign in February.
A win over City would certainly give Victory momentum before they visit Newcastle Jets and Central Coast Mariners in consecutive matches and then host Adelaide United on February 25.
With Roar in the midst of five games in 15 days due to their AFC Champions League (ACL) qualifying campaign, Victory have the chance to solidify their hold on second spot this month.
The benefits of finishing second will be two-fold, as it should ensure an ACL berth for 2018, while also providing the fortunate club with a home semi-final.
With so much on the line, you won't want to miss the fourth Melbourne derby of 2016-17.