The two teams butt heads for the first time since the 2023 Champions League final - their only previous European encounter - when Rodri scored the decisive goal in a narrow 1-0 victory in Istanbul to help the Citizens complete a historic treble.
Match preview
Man City are the only Premier League team who boast a 100% record after four matches, but their perfect start to the new campaign was put to the test by a cohesive, hard-working Brentford side on Saturday.
The Etihad faithful were left stunned when Yoane Wissa capitalised on a mishap from John Stones to head the Bees in front after just 22 seconds, and although the visitors had numerous chances to extend their advantage, Erling Haaland's ruthless finishing before the break was ultimately the difference in a 2-1 victory for the Citizens.
Haaland's double turned the contest on its head just after the half-hour mark, increasing his impressive goal tally for the season to nine - breaking a new Premier League record in the process - as well as moving him onto 99 goals for Man City in just 103 games across all competitions.
Pep Guardiola's side have now extended their exceptional unbeaten record at the Etihad to 46 games (W39 D7) and are now gearing up for three more home fixtures across three different competitions in the space of just seven days, following up Wednesday's Champions League clash against Inter with Premier League and EFL Cup games versus Arsenal and Watford respectively.
Man City will be keen to make a strong start in the newly-expanded Champions League and secure a statement win over Inter; they head into their midweek showdown having not lost any of their last 23 Champions League matches and if they avoid defeat in their opening two fixtures of this season's competition (against Inter and Slovan Bratislava on October 1), they will equal the longest unbeaten streak in the competition's history set by rivals Manchester United (25) between 2007 and 2009.
After beating Lecce and Atalanta BC by an aggregate score of 6-0, Inter Milan were unable to claim their third successive Serie A victory last weekend, as they were forced to rescue a 1-1 draw away against Monza.
The Nerazzurri looked on course to suffer their first defeat of the campaign when Dany Mota headed the hosts into a surprise 81st-minute lead, but Denzel Dumfries came to the rescue for the visitors and netted an equaliser just seven minutes later to salvage a point for the reigning Italian top-flight champions.
Head coach Simone Inzaghi was "disappointed" with the result and rued the number of missed opportunities his side had, particularly in the first half. His players are now tasked picking themselves up for a huge double-header this week against Man City in the Champions League and against bitter rivals AC Milan in Serie A.
Inter head into Wednesday's contest having lost only three of their last 20 Champions League matches (W11 D6). However, the Italian giants have only started one of their last nine campaigns in the competition with a victory.
Seeking revenge against Man City following their 2023 Champions League final heartache, Inter travel to Etihad having previously won away at four different English clubs in the competition (Newcastle United, Arsenal, Chelsea and Liverpool), and they are bidding to become the fourth team after Barcelona (seven), Real Madrid and Bayern Munich (both five) to win on the road against at least five different English teams.
Manchester City form (all competitions):
W
W
W
W
W
W
Inter Milan form (all competitions):
L
D
D
W
W
D
Team News
Man City are still having to cope without attacker Oscar Bobb (leg fracture), while defender Nathan Ake has been ruled out until after the next international break in mid-October with a muscle injury.
Guardiola is expected to hand star lynchpin Rodri his first start of the season after he gained 45 minutes of action under his belt in the win over Brentford, while Phil Foden will also be pushing to start after watching on as an unused substitute last time out.
While few would be surprised to see Haaland - who has remarkably scored 41 goals in just 39 Champions League games - lead the line once again, it remains to be seen whether Guardiola will stick with Kyle Walker at right-back or move Rico Lewis over from left-back and recall Josko Gvardiol, while Ruben Dias, Manuel Akanji and John Stones all battle for a start at centre-back.
As for Inter, versatile wideman Tajon Buchanan is their only injury absentee as he continues to recover from a fractured tibia sustained on international duty with Canada at the Copa America this summer.
Inzaghi is expected to recall a number of key players including defender Alessandro Bastoni and midfield duo Hakan Calhanoglu and Nicolo Barella, the latter of whom watched on as an unused substitute last time out not long after undergoing sinus surgery.
Marcus Thuram has contributed with four goals and two assists in four Serie A games and is set to retain his place up front alongside captain Lautaro Martinez, who is yet to score in three appearances so far this season.
Manchester City possible starting lineup:
Ederson; Lewis, Stones, Dias, Gvardiol; Rodri, Kovacic; Bernardo, De Bruyne, Grealish; Haaland
Inter Milan possible starting lineup:
Sommer; Pavard, Acerbi, Bastoni; Dumfries, Barella, Calhanoglu, Mkhitaryan, Dimarco; Thuram, Martinez
We say: Manchester City 2-1 Inter Milan
A closely-fought contest between two genuine challengers for Champions League glory is set to take place at the Etihad, but Man City's exceptional home form makes them the favourites to come out on top.
The Citizens have been conceding goals in recent weeks which bodes well for Inter, but Guardiola's men have had Haaland to thank for banging in the goals and if his red-hot form in the final third continues on Wednesday, the hosts should ultimately fine a way to prevail.