Roger Schmidt's men have won every single one of their games in Europe since stumbling to last season's Ligue 1 runners-up on Matchday 1, and a successful revenge mission at the BayArena would see them reach their primary goal with a game to spare.
bundesliga.com takes a closer look at die Werkself's latest European mission...
A draw is enough for qualification, but Leverkusen want a fourth straight win in the Champions League to leave no doubt as to who is the leading force in Group C. That result would also earn Roger Schmidt's men a seeding for the round of 16. Monaco, meanwhile, can narrow the gap with victory while defending second spot from FC Zenit and SL Benfica ahead of a decisive final Matchday.
Wendell (pictured) is available again after sitting out a suspension against Zenit last time out, while club captain Simon Rolfes and Gonzalo Castro, who both got a half under their belts in the weekend win at Hannover, are also at coach Roger Schmidt's disposal.
Only Borja Lopez is missing for the Principality side with their coach Leonardo Jardim announcing in the wake of his side's 2-2 draw at home to SM Caen at the weekend that Andrea Raggi, Nabil Dirar and Layvin Kurzawa will all feature after being left out on Saturday. Mercurial striker Dimitar Berbatov (pictured) is set to lead the line.
After ending a run of 859 minutes without a Bundesliga goal on Saturday, Stefan Kießling (pictured) will be keen to add to his four goals in the UEFA Champions League (qualifying included) so far this season and prove he truly is back in form. The 30-year-old has scored a total of seven times in Europe's elite club competition.
Midfielder Jeremy Toulalan (pictured) hinted this week that he may be about to leave Monaco, but the clamour his potential departure has caused is proof of how important the experienced 31-year-old captain is to the club. The skipper pulls the strings in the heart of midfield and was arguably the man of the match in the two teams' previous meeting in September.
Heung-Min Son(pictured, Leverkusen forward): "We're extremely motivated and we've forgotten all about the 1-0 defeat in the reverse fixture."
Jardim (Monaco head coach): "We've got eight games until the end of the year and we need to work hard to get back to winning ways."
Leverkusen climbed to fourth in the Bundesliga with Saturday's 3-1 win over Hannover 96 and they have lost only one of their last 12 games in all competitions, also making good progress in the DFB Cup. Monaco's disappointing draw at the weekend has left them in eighth in Ligue 1, eleven points from the summit.
Before their 1-0 defeat on the Cote d'Azur in September, Leverkusen's last trip to Monaco ended in a 4-0 defeat in the 1997/98 season. They picked up a point at the BayArena with the French side coming from two goals down to snatch a 2-2 draw.
Leverkusen: Leno - Donati, Toprak, Spahic, Wendell - Bender, Rolfes - Bellarabi, Calhanoglu, Son - Kießling
Monaco: Subasic - Fabinho, Ricardo Carvalho, Raggi, Echiejile - Joao Moutinho, Toulalan, Kondogbia - Ferreira-Carrasco, Berbatov, Dirar