Carlo Ancelotti's men hammered their Bundesliga counterparts at the Veltins-Arena in the last-16 first leg a year ago on their way to a historic 10th European title.
Schalke have since changed their coach, with Roberto Di Matteo now the man charged with helping Schalke past their Spanish opponents and into the quarter-finals.
While Di Matteo will be without the likes of Julian Draxler (hamstring), Leon Goretzka (hamstring) and Jefferson Farfan (knee), former Bayern Munich midfielder Toni Kroos - now at Real - warned of the challenge his team-mates will face.
"There are five or six teams that can win the Champions League and we are one of them," he told UEFA outlets.
"We will try to win it but it will be very difficult because how you do in the knockout ties depends very much on your form that day.
"It won't be easy. Schalke are enjoying success in the Bundesliga. They are well organised, they drew in Munich and are strong at the back.
"With their new manager they have become extremely solid in defence. We have injuries so this will be a tough challenge, but our aim is to qualify to the next round."
Real - who lead La Liga by a point from Barcelona - boast a nine-match winning streak in the Champions League and have won seven of their last nine away games in the competition.
Ancelotti's men are bidding to become the first side to retain the Champions League trophy and, despite the absences of James Rodriguez (toe) and Luca Modric thigh), Sidney Sam is under no illusion as to the threat Real will pose.
"They have a world-class squad full of big names like Cristiano Ronaldo, Gareth Bale, Karim Benzema and many more," he told Schalke's official website.
"If we defend in a compact manner, we will make life difficult for any team in the world. We have good players too. I'm certain that we're going to have chances.
"It's a new season, a new situation. I think we are more stable as a team this year.
"Our fans believe in us, we believe in ourselves - these are key features should we wish to succeed against Real."
Sam made his comeback from a long-term leg problem in Schalke's 1-0 defeat at Eintracht Frankfurt on Saturday, while Real could welcome back Pepe this week following a rib injury.
