The Black Stars have confronted the Indomitable Lions four times from 1982 and the best they have achieved is two group draws while suffering two semi-final defeats.
"We are going to give Cameroon a really good game and I am sure we will emerge victorious," said the coach in his second spell as Ghana coach.
Defending champions Cameroon will start as slight favourites to win the Group F clash in Ismailia Saturday having been the more impressive performers earlier this week.
Cameroon scored twice in three minutes to end the resistance of Guinea-Bissau and win 2-0 while Ghana had John Boye red-carded as they were held 2-2 by Benin.
Here, AFP Sport previews the three Saturday matches, with Benin and Guinea-Bissau the other fixture in an Ismailia double-header, while Angola meet Mauritania in Group E in Suez.
Cameroon v Ghana
Appiah is not overly concerned with the two dropped points against lower-ranked Benin because Ghana are traditionally slow starters at the Cup of Nations.
They always recover and boast a record of six consecutive top-four finishes from 2008, including finishing runners-up twice.
He was upset by the dismissal of veteran Boye, believing his time wasting should have earned a verbal warning rather than a second yellow card.
Cameroon centre-back Ambroise Oyongo, one of four starters against Guinea-Bissau who were part of the 2017 title-winning team, says they must improve against Ghana.
"We have to raise our game against Ghana. We did not start with a win in 2017 but this time we did and I believe that is a good omen going forward in the competition."
Benin v Guinea-Bissau
Former English Premier League midfielder Stephane Sessegnon has personal and team ambitions ahead of his probable return to the team after missing the Ghana match through suspension.
The Turkey-based 35-year-old captain of the Squirrels needs one goal to overtake Razak Omotoyossi and become the record scorer for the national team.
He also wants to help Benin finally win a match at the Cup of Nations after two draws and eight losses since debuting 15 years ago.
Another threat to Guinea-Bissau will be physically imposing Mickael Pote, who also plays his club football in Turkey and bagged a brace against Ghana.Â
Guinea-Bissau contained Cameroon for 65 minutes, but once they fell behind to a Yaya Banana header the Djurtus (wild dogs) had little bite in attack.
Angola v Mauritania
These Group E rivals defeated each other at home in qualifying for a 2019 Cup of Nations switched to Egypt after Cameroon fell behind with preparations.
Angola recovered from falling behind after just two minutes to triumph 4-1 in Luanda and Mauritania gained revenge four days later with a 1-0 win in Nouakchott.
Mauritania conceded four goals again this week when losing to Mali and often poorly positioned goalkeeper Brahim Souleimane could be axed by French coach Corentin Martins.
Serbia-born Angola coach Srdjan Vasiljevic was thrilled by the come-from-behind 1-1 draw with Tunisia, who are making a record-extending 14th straight appearance at the tournament.
"We got a good result after enormous difficulties in the preparation period. We want to play good football and compete with the best African teams," he said.Â