Both sides are in form, strolling into the final qualifying round by comfortably topping their respective groups, and will gear up for the first leg of a massive tie in Kumasi.
Ghana's bid to make a third successive World Cup finals will see it meet Egypt in the first leg of their playoff on Tuesday.
The Black Stars will enter the match in good form, having finished four points clear of 2012 African Cup of Nations champion Zambia at the top of qualifying Group D.
The team will be confident of building a lead in the home leg of the playoff, given its superb record in front of its own fans.
Indeed, the Black Stars have not tasted defeat on home soil since going down to Cameroon in Accra during the semis of the 2008 Africa Cup of Nations, though they have not been beaten at the Baba Yara Stadium since 2000, when they lost to South Africa.
However, coach Kwesi Appiah knows his side must not take this opponent for granted in the crucial first leg at the Baba Yara Stadium.
"It's a big game, a game which is important to all Ghanaians," he said. "Every member on my team is aware of that.
"Egypt are seven-time African champions and trying to reach the World Cup for the first time since 1990. That will give them some added boost going into the game. Their record in its sense means that we cannot look down on them. We can't get complacent. We have to prepare well and remain focused."
Appiah will be without one of his stars though, with Schalke attacker Kevin-Prince Boateng (knee) sidelined for the fixture.
Egypt was the only team in the group stage of qualifying in Africa to win all six of its matches, as it cruised into the playoffs on top of Group G.
Bob Bradley's side has played all of its home fixtures behind closed doors because of security concerns in the country, but that has not stopped the players as they bid to reach their first World Cup since 1990.
Egypt has not lost a competitive match since a 3-2 defeat to the Central African Republic in African Cup of Nations qualifying in June 2012, and Bradley is in a bullish mood ahead of the clash.
"We studied Ghana well," said the American coach. "We respect them, but at the same time we are a good team.
"We must be smart in Kumasi. We need to play with the right mentality, intellectually but with confidence."
The top scorers in African qualifying - Mohamed Salah and Mohamed Aboutrika - are both in the Egypt squad for the seventh meeting between the two nations.
Both sides have won against each other on two occasions, with Ghana winning the last encounter 3-0 in January.