The Mauve and Yellows, third on the table, have beaten the Porcupine Warriors in Tarkwa for the past three seasons.
However, the big clash has been overshadowed by a shooting incident which has marred the fantastic start of the Ghana Premier League.
A Kotoko fan was shot by a policeman following rioting scenes in the wake of their 1-0 defeat at home to Berekum Chelsea on Sunday.
Subsequently, Kotoko have been hit with a temporal home ban after the unfortunate fans trouble.
Kotoko must prove their attacking potential against a solid-looking defensive back -four of Medeama comprising Samuel Appiah, Philip Osei, Ibrahim Yaro and Daniel Egyin.
Maxwell Konadu knows how to pull off results on the biggest occasion. If he manages to salvage anything from the Mauve and Yellows own fortress, it's will be the sweetest salvation. However, if things go wrong, a terrible nightmare could unfold for the visitors.
Both teams are heading into the game with contrasting fortunes.
Kotoko have won two and lost once while Medeama have picked seven points from a possible nine.
The Porcupine Warriors must draw up a plan on how to keep Medeama from running riot. If you nullify a problem, a dozen others creep up against a free-scoring side.
Medeama have scored seven goals and conceded two in three games to make their attacking duo of Prince Opoku-Agyemang and Nana Kofi Babil tough customers.
In order to keep the rapturous atmosphere in check, Maxwell Konadu's side must frustrate the hosts into making errors. It’ll be a huge day for both teams who are desperate to return to winning ways.
Medeama goalkeeper Eric Ofori Antwi has already proven his excellence in big games, but must repeat his heroics at the Akoon Park in order to keep Sogne Yacouba and Emmanuel Gyamfi quiet.
The biggest challenge, however, is in store for Medeama young sensation Nana Kofi Babil.
Babil, 17, has scored in opening three consecutive matches from the bench, to make him the youngest playyer to achieve that feat in the Ghanaian top-flight.
He must maintain peak concentration to pile pressure on the Kotoko defensive pair of Wahab Adams and Agyemang Badu.
Medeama trio Richard Boadu, Agyei Boakye and Kwasi Donsu must be diligent enough in closing down their midfielders, making interceptions and protectng their backline from being overloaded.
Kotoko won't be getting a bucket load of chances in Tarkwa but make the few ones that come their way count.
Medeama are determined to move up the ladder and will do their title credentials lots of good if they negotiate a win against the Kumasi-based side.
Medeama predicted XI
Eric Ofori Antwi, Samuel Appiah, Philip Osei, Daniel Egyin, Ibrahim Yaro, Richard Boadu, Agyei Boakye, Kwasi Donsu, Agyenim Boateng, Ebenezer Ackhabi, Prince Opoku-Agyemang.
Kotoko predicted XI
Felix Annan, Christopher Nettey, Moro Ibrahim, Wahab Adams, Agyemang Badu, Justice Blay, Collins Ameyaw, Mudasiru Salifu, Songne Yacouba, Augustine Okrah, Emmanuel Gyamfi.