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Pep Guardiola's side grabbed a 2-1 win in the first leg at the Etihad courtesy of a late winner from Phil Foden after Marco Reus' strike cancelled out Kevin De Bruyne's opener.
City travel to Germany on the back of a shock 2-1 defeat by Leeds United on Saturday, and will be hoping to bounce back with another strong performance in Europe.
Meanwhile, Dortmund took all three points in a 3-2 win at Stuttgart on the weekend as their inconsistent season continues to take twists and turns ahead of a fixture that is arguably their biggest of the campaign to date.
And the German giants will be hoping Erling Haaland can end his goal drought after failing to score in his last six games for club and country - his longest barren run since moving to the Bundesliga.
Marco Reus's away goal may prove vital against City, especially with Jadon Sancho still not fit enough to face his former club.
Borussia Dortmund found a chink in Manchester City's armour last week to stoke belief that a previously impossible-looking upset might be on.
Two goals are the minimum requirement for Dortmund, who will be hoping Erling Haaland can end a run of 495 minutes without a goal for club and country.
City hold the advantage, but need to stay focused and avoid the defensive mistakes which have cost them so dearly at this same stage in the past three seasons under Guardiola.
If they do that, a first UEFA Champions League semi-final since 2016 is within their reach.
Former Manchester City youth product Jadon Sancho will not be reuniting with the Citizens this week as he remains sidelined with a thigh problem, and two new faces in Marco Reus and Mats Hummels have joined the England international in the treatment room.
On the other hand, City's treatment room has been unoccupied for the past few weeks, but Sergio Aguero and Aymeric Laporte have suffered fresh injuries and are not expected back in time for the second leg.
As he so often does, Guardiola made a raft of changes for the defeat to Leeds, and two alterations in the rearguard should see Ruben Dias and Kyle Walker return for Nathan Ake and Benjamin Mendy.
Fernandinho and Oleksandr Zinchenko started in midfield at the weekend, but will make way for Rodri and Ilkay Gundogan here, with Riyad Mahrez, Phil Foden and Kevin De Bruyne completing an overhaul in attack.
Borussia Dortmund are 4/1 to win in midweek, with Manchester City priced at 8/13 to come away with victory. A draw is priced at 16/5.
Odds are correct at the time of publication and are subject to change.
Manchester City are aiming to reach the Champions League semi-finals for the first time in five years against Borussia Dortmund on Wednesday night.
BT Sport will be televising the match and BT subscribers will also be able to watch the match online via the website or the BT Sport app.
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