Antonio Conte's side are currently bottom of the group while their German opponents lead the way on goal difference ahead of Barcelona.
Fresh off ending their two match winless run at the weekend, Inter enter Wednesday's game looking for their first win in this year's Champions League.
Although Inter looked good going forward against Sassuolo, they had some hairy moments defensively in the second half which made things far closer than they really should have been.
Samir Handanovic conceded three from the four shots on target he faced in that game and he, along with the defence that played on Sunday, have since been heavily criticised by Conte for their performance.
One positive from that game was the budding partnership between Romelu Lukaku and Lautaro Martinez, and their combination of pace, power and quality finishing will be essential against a Dortmund defence that has kept a clean sheet in seven of their last eight games in the Champions League.
While Inter won 4-3 on aggregate when these sides last met, that was all the way back in 1994 and more recently the Nerazzurri have struggled against German opposition, losing five of their last six against them.
While the Black and Yellows are averaging 2.5 goals a game in German league action, Lucien Favre's side have lacked their usual cutting edge in their opening Champions League matches, scoring just twice.
Although Inter's performance at the weekend suggested that Dortmund will get chances to score on Wednesday, the Germans will need to play at pace to get in behind the Italian side's midfield enforced Marcelo Brozovic, who has reached a new level in recent months.
Dortmund are currently top of the Champions League group and while they will know that a win over the Italian side in such a tight group will put them in pole position to qualify for the last 16, they may opt to set up a little more conservatively on Wednesday given their upcoming schedule.
Favre's men still have league fixtures against Schalke, Wolfsburg and Bayern Munich before the international break, as well as a rematch with Monchengladbach in the German Cup and the return game against Inter.
With that in mind, the traditionally attacked-minded team may be more content with a draw away from home that conserves their resources ahead of a tough run that could have a major impact on their season.
Inter Milan recent form: DL
Inter Milan recent form (all competitions): WWWLLW
Borussia Dortmund recent form: DW
Recent form (all competitions): DDDWDW
Dortmund also have a largely clean bill of health aside from Paco Alcacer, although Swiss keeper Roman Burki went off during the weekend's game and Marwin Hitz is likely to take his place for this game.
The main selection dilemma for the Germans will be whether to recall Jadon Sancho, who was dropped from the squad for the Monchengladbach game after reporting back late from international duty.
Should the Englishman be recalled, Favre will probably go for a 4-2-3-1 with Sancho on the right and Achraf Hakimi at right-back, but if not then the Moroccan would likely be pushed into midfield with Lukasz Piszczek coming into the defence.
Inter Milan possible starting lineup:
Handanovic; Skriniar, Godin, De Vrij; Brozovic; Candreva, Gagliardini, Barella, Asamoah; Martinez, Lukaku
Borussia Dortmund possible starting lineup:
Hitz; Hakimi, Akanji, Hummels, Schulz; Delaney, Witsel; Sancho, Hazard, Brandt; Reus
We say: Inter Milan 1-1 Borussia Dortmund
Given the recent performances of both sides, this game could either be very tight or wide open, but home advantage for Inter should be enough to secure them at least a point.