Manchester City v CSKA Moscow: Win-or-bust for hosts in UEFA Champions League bid
The Premier League champions head into the encounter in high spirits after claiming city bragging rights by beating neighbours Manchester United on Sunday, with Aguero scoring the only goal in a 1-0 win at the Etihad Stadium.
However, while that victory kept them in the early title race behind leaders Chelsea domestically, in Europe their position is far more precarious.
Manuel Pellegrini's side are third in Group E with only two points to their name after a disappointing opening.
Defeat at Bayern Munich on matchday one was followed by a 1-1 draw with Roma and a 2-2 scoreline in Moscow last time out, with City conceding twice late on at the Arena Khimki having forged a two-goal lead.
That leaves them staring at a group-stage exit for the third time in four seasons, and while defeat in the return fixture against CSKA would not mathematically end their hopes, it would leave them needing a near miracle to qualify.
Speaking after his match-winning contribution against United, Aguero was quick to stress the importance of Wednesday's clash.
"I think Moscow is the most important game because we have to win," he told the club's official website.
"I think it is very important and I think we have the squad to win it. We have to get the three points and then do the same in the last two remaining games."
Pellegrini's men will at least have a vocal sell-out support at the Etihad, after the reverse fixture was played behind closed doors as a result of a UEFA sanction on CSKA for racism and crowd trouble.
On the pitch, City could also be boosted by the return to action of Frank Lampard, who is close to a comeback after being sidelined since the middle of last month by a leg injury.
David Silva will not feature as a result of a knee problem, while full-back Aleksandar Kolarov is a major doubt after missing the Manchester derby when limping out of the warm-up.
CSKA are still without injured Swede Rasmus Elm (stomach) and Kirill Panchenko (knee), but Vitinho is available again after an ankle problem that has kept him out since August.
Pontus Wernbloom and Alan Dzagoev are expected to be restored to the squad after returning from suspension.
Coach Leonid Slutsky could opt to change his attacking options following a 1-0 Russian Premier League defeat to leaders Zenit on Saturday, conceding after that match: "We had chances to score, especially in the second half, but missed all of them."