In the opening fixtures of Group A, the Indomitable Lions saw off Zimbabwe 1-0, while Nouhoum Diane's men defeated Burkina Faso by the same scoreline.
Cameroon are the host nation for the sixth edition of the tournament, and Martin Ndtoungou Mpile's side will be hoping they can use home advantage to claim the trophy for the first time.
Mpile is embarking on his second spell in charge of the central African nation after leading them to the quarter-finals of the 2016 African Nations Championship in Rwanda.
The Indomitable Lions have reached the last eight of the competition on two previous occasions but were knocked out in the group stages when Morocco hosted in 2018.
Charles Banga's goal was enough to secure their first victory last time out, and the pre-tournament favourites will be keen to establish their dominance over the group with another victory in midweek.
Mali were beaten finalists four years ago, losing 3-0 to the Democratic Republic of the Congo, who won their second CHAN title.
Siaka Bagayoko's strike was enough to get the better of Burkina Faso on Saturday and move joint-top with Cameroon, giving the Eagles genuine belief that they can progress to the knockout stages.
Diane guided Stade Malien to six Premiere Division successes during his time with the club, and it is hoped he can replicate that success on the international scene.
Three points on Wednesday would be a huge boost to their chances of finally lifting some silverware and would fill this inexperienced Mali side with confidence for the rest of the competition.
Cameroon African Nations Championship form: W
Cameroon form (all competitions): WWDLLW
Mali African Nations Championship form: W
Mali form (all competitions): WWWWWW
Mpile is unlikely to make many changes from the starting XI that defeated Zimbabwe, meaning Bryant Soga is set to lead the line once again.
Forward Moussa Kone is the danger man for the Eagles, and the AS Real striker will be eager to get his first goal of the competition in midweek.
Cameroon possible starting lineup:
Kerrido; Mamoudou, Banga, Matanda, Andoulo; Oukine, Tchuente; Etong, Zoua, Assomo; Soga
Mali possible starting lineup:
Diarra; Samake, Diarra, Sidibe, Ballo; Sissoko, Kyabou, Samabaly, Kanoute; Kone, Coulibaly
We say: Cameroon 1-1 Mali
It should be a tight affair between two evenly matched teams that are desperate not to let the other side gain an advantage over them. Therefore, we can see this ending in a low-scoring draw as both teams settle for a share of the spoils.