Atletico go into the game as defending Liga champions.
It remains to be seen if Simeone can work his magic again, but with Real and Barcelona both spending big this summer to bring in players such as Luis Suarez, James Rodriguez and Toni Kroos, the Argentinian is well aware of the task facing his side.
When asked about his objectives ahead of Tuesday's Supercopa first leg against Real at the Bernabeu, Simeone said: "The objective, talking about the Supercopa, is to try to get the game to where we want it, and obviously win it.
"Regarding the league. We have four different players with respect to last year. It's a major change, because their characteristics are not the same and the adaptation time is very short.
"We'll see throughout the season where the team can get to, but right now our reality is to look at Sevilla, Valencia, Athletic (Bilbao)...who are the teams with whom we will try to fight for a place in the Champions League."
He added of his side's summer spending compared to Real's: "We've spent 95 million on bringing in seven or eight players, they spent 95m on two.
"Real Madrid have improved, the presence of Kroos gives then even better potential in the middle of the pitch, more stability, balance and passing. What we've seen of (Gareth) Bale is much better than when he started, which makes him more dangerous in attack.
"It's a better team than last season."
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