The Die Werkself, who had finished third in their group last term behind Barcelona and AS Roma, have been pitted alongside the likes of Monaco, CSKA and Premier League giants Tottenham Hotspur this season.
The group, which is likely to see Mauricio Pochettino's side go through, presents Schmidt's men with the opportunity to make it to the knockout rounds for the second time in three years.
A familiar platform beckons
The men from the Russian capital, who featured in Europe's elite tournament last season and were placed in Group B alongside Wolfsburg, PSV Eindhoven and Manchester United, have made a steady start to their Russian Premier League campaign. The Red Horses currently lie second in the table, behind city rivals Spartak Moscow and have drawn two games, losing none.
Finnish midfielder Roman Eremenko, who has been deployed right behind towering forward Lacina Traore in a 4-2-3-1, has turned out to be rather unexpected star performer thus far, scoring thrice and racking up two assists in six league games.
Leverkusen, on the other hand have made a rather indecisive start to their Bundesliga campaign, having won one and lost one in two games. Saturday's clash at BayArena saw young Joel Pohjanpalo grab a stunning hat-trick, to send Hamburg packing in an impressive 3-1 comeback triumph.
An opening day loss against Andre Schubert's Borussia Monchengladbach, who are placed in the same group as Barcelona, Manchester City and Celtic, saw an Andre Hahn brace eclipse Charles Aranguiz's early strike. The Werkself currently lie at 7th in the Bundesliga, after finishing as high as third last season.
Bayer look to find their form
New signing Kevin Vollland, who fractured his finger earlier this month, is a doubt for the game and Karim Bellarabi, who was taken off for young Julian Brandt against Hamburg at the weekend, is likely to miss the outing. The German winger, who was a key outlet for goals for Schmidt last season, has suffered a torn muscle fibre and is reportedly to spend some time on the side lines, with Schmidt having said after the game that he could be ruled out till October.
The 4-4-2 formation, that saw Chicharito and Hakan Calhanoglu start up front, ended up acting as a success mantra last season, albeit with lack of midfield depth and mobility up front. The capture of Julian Baumgartlinger, who made his debut against Gladbach three weeks ago, adds more steel in the heart of the park and could well start on Wednesday. Vladen Yurchenko and Robbie Kruse will not start but a shift to the familiar 4-2-3-1 with Calhanoglu wide and Pohjanpalo up front would be a rather feasible thing to do, especially at home.
Can CSKA prove their European mettle?
Leonid Slutsky's men could win only one game during their Champions League campaign last season, losing four times and drawing once against Louis van Gaal's Manchester United at home. The loss of Ahmed Musa to Leicester City made sure that CSKA lost a lot of pace at the break, but Lacina Traore brings in different dimension to their play. He allows CSKA to be more direct than they were last season, thanks to the hold up and heading abilities that the former Monaco man brings to the plate.
The 4-2-3-1 formation, that involves Russian centre half pairing Sergei Ignashevich and Vasili Berezutski, did really well for the capital side against United at Old Trafford and at the Khimki Arena too as the back four held its line very well. The pace on the break and compactness in the midfield is something that turns CSKA Moscow into a rather frightening side to handle at Khimki. But this game in Germany could prove to be a tough one.
Injury concerns hampering Leverkusen
As already mentioned, Leverkusen have got a whole list of players at the nursing table, while CSKA Moscow have a near-fit squad with the exception of Aleksandrs Cauna, who underwent a foot surgery some weeks ago and is expected to return next week.
Solid defensive performance key for Schmidt
CSKA's approach to the game will be direct, with Traore likely to feature up front and Leverkusen would have to keep him quiet throughout the game, with their attack looking good enough to score past a majority of Bundesliga sides, not just CSKA Moscow. And the duo of Omer Toprak and young Jonathan Tah would have to be aware of the physical and aerial presence that Traore offers, if balls are fed to him.
CSKA are always known to be a side which is good in the air and can be very effective, when it comes to defending set pieces. Ignashevich and Berezutski and defenders who are strong and aerially robust, much like Traore and midfield dynamo Pontus Wernbloom. And Leverkusen would have to be vary of the threat that Slutsky's hard-working men in red pose from dead ball situations.
Bayer Leverkusen (4-4-2): Leno; Jedvaj, Toprak, Tah, Wendell; Calhanoglu, Baumgartlinger, Kampl, Mehmedi; Pohjanpalo, Chicharito.
CSKA Moscow (4-2-3-1): Akinfeev; Mario Fernandes, V. Berezutski, S. Ignashevich, Shchennikov; Wernbloom, Dzagoev; Tosic, Eremenko, Golovkin; Traore.