A win for Roger Schmidt's team will guarantee top spot in the highly competitive Group C, while a draw will be enough to secure a spot in the last 16.
Leverkusen fans may be expecting their side to progress from the group stage for the third time in four seasons, having enjoyed an unbeaten start at home since Schmidt arrived from Red Bull Salzburg in pre-season.
Six wins and three draws from nine outings on home soil have helped Leverkusen to fourth in the Bundesliga and first place in their Champions League pool, where each side can still go through.
A 3-1 win over Hannover on Saturday also brought relief to the BayArena faithful as striker Stefan Kiessling ended a 10-game and 859-minute goal drought domestically and Schmidt expects that breakthrough to prompt a change in mentality for the 30-year-old.
"The goal was valuable, it gives him peace," he is quoted as saying by Bild. "The discussion is over.
"Even if he had not scored a goal, he once again had a great game."
Monaco are the only side to avoid defeat to Leverkusen in this year's competition after a 1-0 victory at Stade Louis II, but Joao Moutinho's winner in that game is their only goal in the group stage so far.
A pair of goalless draws and a 1-0 defeat at Benfica last time out leaves Monaco perilously close to the Portuguese side and Group C's other team, Zenit.
Their European form is largely reflected in Ligue 1, where Monaco have drawn four of their last six games to leave them in eighth – well adrift of the league's leading pack of Paris Saint-Germain, Marseille and Lyon.
Coach Leonardo Jardim has constructed a youthful side since losing star names such as James Rodriguez and Radamel Falcao, but concedes his players have plenty to improve upon before they become the challengers at home and abroad they were expected to be after being bankrolled back into contention.
He told Canal+: "Sometimes they still have to learn. We grant them too easily a star status, but I think youngsters are not that professional.
"You have to remind them of training times, discipline and the needs of the job.
"They have the chance to play in the first team and they think they have made it."
Wendell returns to Leverkusen's European squad after serving a one-game ban last time out while Simon Rolfes and Gonzalo Castro's returns from injury against Hannover give Schmidt a further boost, but Stefan Reinartz (eye socket) and Kyriakos Papadopoulos (knee) are out.
Former Leverkusen striker Dimitar Berbatov returned from a thigh injury in Monaco's 2-2 draw with Caen this weekend, but Layvin Kurzawa remains sidelined with a similar complaint.
