Antonio Conte's men are yet to register their first victory in European competition this season, but the Serie A powerhouses did manage to get a vital three points on the board in the league as Torino fell victim to a 4-2 defeat at San Siro at the weekend.
Sitting rock bottom of Group B, Inter's first meeting with Real earlier this month saw the Spaniards run out 3-2 winners at the Estadio Alfredo Di Stefano, with the Nerazzurri's hopes of qualifying for the knockout stages already in jeopardy ahead of this crunch match with Real Madrid.
Here, Sports Mole looks at how Conte could line his side up for the visit of Real Madrid on Wednesday evening.
This is a must-win game for Conte's Inter as they look to avoid falling at the first hurdle in the Champions League, and that is sure to be reflected in the Italian's team selection.
The hosts will be without the COVID-positive trio of Aleksandar Kolarov, Marcelo Brozovic and Daniele Padelli for this one, while Stefano Sensi and Matias Vecino continue to nurse injuries.
Conte has big calls to make when it comes to who will be protecting veteran goalkeeper Samir Handanovic, but Milan Skriniar and Stefan de Vrij should come back into the side to link up with Alessandro Bastoni, which would demote Danilo D'Ambrosio and Andrea Ranocchia - both starters against Torino - to the bench.
One thing that never changes despite Inter's stuttering form is Conte's loyalty to the 3-5-2, and Achraf Hakimi is sure to start on the right-hand side of the midfield against his former club, while the more attack-minded Ivan Perisic may be given the nod on the left over Ashley Young.
The midfield three of Arturo Vidal, Nicolo Barella and Roberto Gagliardini is likely to remain the same, with Radja Nainggolan yet to start for Inter this season and the out-of-favour Christian Eriksen finding himself linked with a move to Manchester United following his well-documented struggles since arriving in Italy.
Up top, the prolific Romelu Lukaku will be hoping to reach double figures for the season when Real Madrid come to San Siro, and the 27-year-old will likely be partnered by Lautaro Martinez, who came off the bench to bag Inter's fourth in the dying embers against Torino.