The match in Port Elizabeth could dictate who advances from a tough section that also features five-times World Cup winners Brazil and the tournament's most mysterious side North Korea.
Portugal have a lot to prove after a patchy journey to the finals and doubts remain over whether the influential Pepe is ready to start after a lengthy injury layoff.
There are also question marks about Cristiano Ronaldo's ability to replicate his potent performances with Real Madrid at the World Cup after mediocre displays in the qualifiers.
Although the Ivorians have plenty of talent, the absence of the inspirational Drogba, who scored an eye-popping 37 goals for Chelsea in all competitions last season, could complicate their chances of reaching the second round for the first time.
With no easy matches in the group, the key question facing their Swedish coach Sven-Goran Eriksson is whether the Elephants can afford to hold Drogba back for later games.
The striker has resumed training after having surgery on a broken arm sustained on June 4 but Eriksson might have to draw on his contingency plans if his leading marksman is not fit.
Kolo Toure, who will captain the team if Drogba does not play, believes younger players like Salomon Kalou and Seydou Doumbia have the ability to step into the void.
"The Ivorian squad is made up of some world class players but football remains a team game," Toure said. "Since he has taken over the squad, the coach has been trying to build a proper team and we are on track."
FIERCE CAMPAIGN
Eriksson knows Portugal only too well after they eliminated his England side in penalty shootouts at the quarter-final stage of Euro 2004 and the last World Cup in Germany.
Portugal are braced for a fierce campaign and a tricky opener against an Ivory Coast side that even without Drogba can boast top class talent like Kolo and his brother Yaya Toure as well as Kalou, Didier Zokora and Emmanuel Eboue.
Portugal's 30-year-old winger Simao Sabrosa is desperate to start and eager to dispel doubts about his pace after a draining 70-game season with Atletico Madrid and the fine form of his possible replacement Danny in recent warm-up games.
Simao insists he is worth a start in Tuesday's match in the blustery coastal city, which he said could go either way.
"We will enter as a strong, positive team. It depends on the first minutes. It will be a tactical game and I think the team that has the most possession will win," Simao said.
"We believe in ourselves. We had lots of problems reaching this World Cup, so we want to make the most of it."
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