Tornadoes lost 2-1 at home, meaning they must not only win in Conakry but score at least twice to avoid an unexpected early exit from the second-tier club competition.
"Nothing is impossible," stresses goalkeeper Aliko. "We were better than Santoba in the first match and now we know all about them."
AFP Sport highlights five clubs hoping to win their first ties in the African equivalent of the UEFA Europa League.
Overall victories by Mauritian clubs in Africa are rare, but Bolton City have a realistic chance after building a 3-1 home lead over Jwaneng Galaxy of Botswana.
The first leg finished dramatically with Patrick Kaunda scoring for the visitors in stoppage time only for Giano Li Tien Kee to restore the two-goal advantage of the hosts.
A first leg shock was Buildcon from central Zambian city Ndola losing 1-0 at home to Young Buffaloes from eSwatini (formerly Swaziland) with Mpendulo Dlamini scoring the late first half winner.
But Buildcon coach and former Zambian international Tenant Chembo believes his team can turn the tables despite doubts about the fitness of Ghanaian defender Eric Owusu.
"We hope Eric recovers in time, but we have depth in the squad and the positivity among the boys leads me to believe we will succeed despite losing at home."
South African second-tier club TS Galaxy caused a sensation in South Africa when they lifted the 2019 Nedbank (FA) Cup after defeating a Kaizer Chiefs side roared on by a capacity 50,000 crowd in Durban.
Apart from a seven million rand ($460,000/415,000 euros) cheque, success secured Galaxy from the northern Mpumalanga province a place in the Confederation Cup.
They debuted in Africa with a 1-0 home win over Saint Louis Suns United from the Seychelles with Sizwe Mdlinzo the match-winner, and will hope missing a penalty does not prove costly.
Mogadishu City Club are the first team from strife-torn Somalia to compete in the Confederation Cup, which was launched in 2004 as the successor to the African Cup Winners Cup and CAF Cup competitions.
Because the Confederation of African Football considers Mogadishu unsafe for visiting clubs, City were forced to play Malindi twice in Zanzibar and drew their 'home' match 0-0 two weekends ago.
That result offers a glimmer of hope for the Somalis because they do not need to win the return match to book a last-32 place -- a score draw will take them through on away goals.
Nigerian clubs are usually too strong for Guinean opponents, so Santoba winning a showdown between Confederation Cup debutants in Kaduna was a shock.
It could have been even worse for Tornadoes as Usmane Kamara and Ibrahim Babawo scored for the visitors before Godwin Zaki pulled one goal back from a penalty.
No Nigerian club has won the Confederation Cup with Dolphins (now Rivers United) coming closest by reaching the 2005 final.