Nouhoum Diane's men saw off Congo in the last round following a penalty shootout, while the Syli Nationale defeated Rwanda 1-0.
Les Aigles progressed from the group stage of the competition after topping Group A thanks to two wins a draw from their three outings.
Diane's side have the best defensive record in the championship, having only conceded one goal to date, and will be hoping to secure their fourth clean sheet in midweek.
Their best performance in the competition came back in 2016 when Les Aigles were defeated in the final 3-0 by the Democratic Republic of the Congo.
Mali will be hoping to go one better this time around and secure the trophy for the first time in their history and will be confident of doing just that after putting in some impressive performances so far.
Guinea topped Group D after picking up five points from their group stage fixtures.
Kanfory Mohamed Bangoura's men have reached the last four of the tournament for just the second time and will be looking to progress to the final for the first time ever.
Star striker Yakhouba Gnagna Barry will be crucial to their chances. The 22-year-old forward has bagged three goals in four games, making him the joint-top scorer in the competition.
Mali African Nations Championship form: WDWD
Mali form (all competitions): WWWDWD
Guinea African Nations Championship form: WDDW
Guinea form (all competitions): DLWDDW
Diane has the luxury of a fully-fit squad to choose from on Wednesday, as Mali have a clean bill of health and no suspended players.
Midfielder Kante is suspended for this semi-final clash following his dismissal last time out.
That means Mohamed Lamine Soumah could be recalled to the starting lineup in order to make his second appearance of the tournament.
Mali possible starting lineup:
Diarra; Samake, Y. Doumbia, M. Doumbia, Bagayoko; Diallo, Kyabou, Kanoute, Sidibe; Ballo, Kone
Guinea possible starting lineup:
M. Camara; N. Camara, Doumbouya, A. Camara, Mohamed Bangoura; I. Camara, Sylla, Soumah, Coumbassa; Mamadouba Bangoura, Barry
We say: Mali 1-0 Guinea
The result of this semi-final is likely to come down to who comes out on top between Mali's defence and Guinea's attack. We fancy Diane's men to get the job done and reach their second African Nations Championship final in five years.