For a ticket to the Qatar 2022 FIFA World Cup, Augustine Eguavoen's side must overcome Otto Addo's charges over both legs, starting from the first leg at the Baba Yara Stadium on Friday.
Eguavoen has invited a total of 25 players to do battle, with a fine mix of experience in Ahmed Musa and Odion Ighalo, form in Victor Osimhen and Calvin Bassey, and talent in Ademola Lookman and Akinkunmi Amoo.
The Super Eagles camp is brimming with so much talent and ability such that Eguavoen has adequate cover for every position on the pitch.
Leicester City midfielder Wilfred Ndidi and Sparta Rotterdam's goalkeeper Maduka Okoye are the only high-profile absentees for the Super Eagles.
However, Eguavoen has a full slate of attackers to choose from with Victor Osimhen, Odion Ighalo, and Emmanuel Dennis all available for this fixture after the trio missed out on the 2021 Africa Cup of Nations (AFCON).
Ahead of the match, we look at Eguavoen's possible line-up against the Black Stars with the 54-year-old tactician expected to stick to his 'Guardiola-style' 4-3-3 formation.
Goalkeeper
Super Eagles' first-choice goalkeeper Okoye is unavailable as a result of illness and Enyimba's John Noble has been invited to the squad in his stead.
Eguavoen is expected to turn to Omonia Nicosia's Francis Uzoho in between the sticks for the doubleheader.
Uzoho has played 13 times for his club side this season, keeping three (3) clean sheets across all competitions.
Defenders
Eguavoen has big calls to make in defence against the Ghanaians, specifically with the Rangers' duo of Leon Balogun and Calvin Bassey.
Balogun is back with the squad after missing AFCON 2021 due to injury but in his absence, Leganes' Kenneth Omeruo had an impressive outing on the continent.
Uncapped Bassey has also been called up to the national team again but this time as perhaps the most in-form Nigerian defender following his impressive performances for Rangers this season.
The 22-year-old would inevitably make his debut for the Super Eagles sometime against the Ghanaians but we will wait to see if Eguavoen would make the big call of replacing the relatively underperforming but familiar Zaidu Sanusi with the high-flying but newbie Bassey at left-back.
For the two big decisions in defense, we expect Eguavoen to revert to the 'Oyinbo Wall' by slotting Balogun back to his starting centre-back role while Sanusi gets the nod ahead of Bassey at least for this first leg.
The remaining two defensive positions pick themselves as captain William Troost-Ekong is expected to take his place in the centre of defence while Torino's Ola Aina should reprise his right-back role for the Super Eagles.
Midfielders
The Super Eagles midfield is bound to look different against the Ghanaians with the absence of Ndidi and Alex Iwobi due to injury and suspension respectively.
Brentford's Frank Onyeka is likely to start in Ndidi's place, providing the anchor and screen for Eguavoen's side.
Rangers' Joe Aribo should take his place in the attacking midfield role again while Leicester City's Kelechi Iheanacho should get the nod to start in the hole just behind the forward players.
New invitee Ademola Lookman could be a second-half replacement for Iheanacho with his direct running and pace capable of carving a potentially tiring Ghanaian defense in the latter stages of the game.
Forwards
The Super Eagles are more than fully stocked in the attacking positions with a full roster of strikers and forwards to prosecute this game against the Black Stars.
Napoli hotshot Victor Osimhen should lead the line for the Super Eagles, coming in in hot form with four goals in his last two league matches in the Serie A.
AFCON hero Moses Simon and Villarreal's Samuel Chukwueze should start either side of Osimhen in the attack.
However, Nigeria's real strength in attack would come in the quality replacements Eguavoen can call on with Al Hilal's Odion Ighalo and Watford's Emmanuel Dennis both destined to come on at some point in the match.
Nigeria's Possible Starting XI against Ghana
Francis Uzoho; Ola Aina, William Troost-Ekong, Leon Balogun, Zaidu Sanusi; Frank Onyeka, Joe Aribo, Kelechi Iheanacho; Samuel Chukwueze, Victor Osimhen, Moses Simon