The Liga high-fliers get their UEFA Champions League campaign under way with a difficult clash against the Russians at the Estadio Vicente Calderon, and they will be looking to build on their solid start to the campaign.
Simeone's men have enjoyed a superb start to their La Liga season, picking up four straight wins to keep pace with Barcelona at the top of the table.
Zenit have also enjoyed an impressive unbeaten run this term, avoiding defeat in their last 10 games in all competitions, and Simeone insists that his side must be ready for the challenge.
He said: "Zenit are an important team. They have economic power and they have the experience of taking part in the Champions League last season.
"They have important players and we must be aware of that. We have to talk in the dressing room and try to sort things out (on Wednesday).
"We know each other and we prefer to think about it match by match.
"At the beginning, the favourites in the group are Zenit and Porto. Hopefully we are going to play in the Champions League more but we have to be realistic and Zenit and Porto have participated more than us.
"It's obvious we are growing and if we face the Champions League with humility we will have our chances."
