While Inter are unbeaten and sit safely inside the top eight, their German counterparts have yet to pick up a point in this season's league phase.
Match preview
After kicking off their latest Champions League challenge with a gritty 0-0 draw at Manchester City - their nemesis in the 2023 final - Inter have since beaten Red Star Belgrade and Arsenal at San Siro, either side of a 1-0 win over Young Boys in Switzerland.
Having kept Mikel Arteta's men scoreless last time out, the Italian giants are yet to concede a single goal in Europe's top club competition this term; another blank on Tuesday would equal Manchester United's run in 2010, when they were the last team to start with five successive shut-outs.
As Hakan Calhanoglu's first-half spot-kick ultimately secured the points against Arsenal, Inter are now unbeaten in 11 Champions League home games, while winning nine and keeping nine clean sheets.
Such a formidable record has helped them reach the knockout rounds for three seasons straight, and Simone Inzaghi's side occupy fourth place in the table midway through this season's league phase.
Although there has been the occasional aberration domestically, the Nerazzurri produced another clean sheet on Saturday, when they scored five goals in the first half of a Serie A away game for just the second time ever, with Marcus Thuram bagging a brace in their 5-0 thumping of Hellas Verona.
Just before the international break, Inter came from behind to draw 1-1 at home with title rivals Napoli, and that is the only goal they have conceded in five matches since an incredible eight-goal Derby d'Italia.
With just one loss in 16 games this season - against old foes AC Milan in September - the three-time European champions will now encounter their 14th different German opponent to date, as they meet Leipzig for the very first time.
While Leipzig are preparing for their first Champions League contest on Italian soil, they have previously beaten both Napoli and Atalanta BC in the Europa League and will not be intimidated by a trip to Milan.
However, they have left no room for error during the second half of their league-phase campaign, as they face automatic elimination following four losses on the bounce.
After going down 3-1 at Celtic Park last time out, Die Roten Bullen are one defeat away from equalling their longest losing run in UEFA's elite competition, and they may end up reflecting on what might have been.
Marco Rose's side have effectively dropped no fewer than nine points from winning positions so far, coming away empty-handed from three games in which they scored the opening goal - versus Atletico Madrid, Juventus, and then Celtic.
Such problems retaining a lead seem to have afflicted some previously excellent domestic form: away from the Champions League, they have lost just twice in 24 games, but both defeats have come during their last three Bundesliga matches, including Saturday's slip-up at Hoffenheim.
Leipzig led three times but still ended up on the wrong side of a seven-goal thriller, with the four goals they shipped being only one fewer than across their first 10 league games combined.
Long-serving goalkeeper Peter Gulacsi had not conceded in the Bundesliga for 510 minutes earlier this season - setting a new club record - but recent lapses will cause some concern. Nonetheless, the Saxony side still sit third in Germany's top flight and can now revel in the underdog role at San Siro.
Inter Milan Champions League form:
D
W
W
W
Inter Milan form (all competitions):
D
W
W
W
D
W
RB Leipzig Champions League form:
L
L
L
L
RB Leipzig form (all competitions):
W
W
L
L
D
L
Team News
After Inter captain Lautaro Martinez returned late from Argentina duty and was then hit by a virus, it remains to be seen whether he will be ready to partner Marcus Thuram on Tuesday; therefore, Mehdi Taremi, Marko Arnautovic and Joaquin Correa - the latter of whom scored on a rare start at the weekend - will all vie for places up front.
Likewise, midfield schemer Hakan Calhanoglu sustained a thigh injury while with Turkey and missed Saturday's win, so Kristjan Asllani is on standby to deputise; Francesco Acerbi went off early in Verona and may also miss out.
Should the veteran centre-back be sidelined, either Benjamin Pavard or Stefan de Vrij would come into the hosts' back three, lining up in front of Swiss goalkeeper Yann Sommer, who has saved all 14 shots on target he has faced in this season's Champions League.
Meanwhile, Leipzig duo Eljif Elmas and Yussuf Poulsen both picked up injuries on international duty, and El Chadaille Bitshiabu recently suffered a setback in training.
Influential playmaker Xavi Simons and Germany full-back David Raum have also been on the treatment table - in their case, due to ankle issues. In the absence of Simons, Christoph Baumgartner has stepped into the breach, and he should support a potent front pairing of Lois Openda and Benjamin Sekso.
With three goals, the latter is Die Roten Bullen's top scorer in the Champions League this term, while winger Antonia Nusa is also enjoying a purple patch: he scored three times in Norway's two UEFA Nations League games this month, then again at the weekend.
Inter Milan possible starting lineup:
Sommer; Bisseck, De Vrij, Bastoni; Dumfries, Barella, Asllani, Mkhitaryan, Dimarco; Thuram, Taremi
RB Leipzig possible starting lineup:
Gulacsi; Klostermann, Orban, Lukeba; Henrichs, Haidara, Seiwald, Nusa; Baumgartner; Openda, Sesko
We say: Inter Milan 2-1 RB Leipzig
Even a steadfast Inter defence may be unable to keep Leipzig at bay for 90 minutes, given the visitors' abundance of pace and finishing prowess.