The derby carries particular significance because of Real’s recent difficulties at the Metropolitano, where they have won only two of their past 11 away matches, with the last in La Liga four years ago.
Atleti also won the corresponding derby last season 5-2 – a result that represented an early setback for Real’s previous project under Xabi Alonso.
This time, though, there is a different manager on the touchline.
Mourinho’s return this summer has brought a familiar emphasis on organisation and adaptability, but he insisted his tactical approach is dictated by the players available to him rather than a fixed philosophy.
“I’ve evolved alongside my players,” he said. “You have what you like and don’t like as a manager but then you have to work with the group of players you have.”
Simeone’s assessment of Real’s biggest weapon was clear.
“They’re better in transition than us,” said the Argentine, who has managed Atleti in over 800 games since taking charge in 2011.
He believes Real’s ability to turn winning the ball into instant attacking opportunities will be one of the key tactical elements in the game.
“When there’s a loss of possession, they look for [Kylian] Mbappe and Vinicius Jr, they play to that strength,” added Simeone.
“We have to read the game well and not allow any turnovers, so we don’t allow them to use those transitions.”
It is a warning that carries weight given the attacking options and speed available to Mourinho.
France striker Mbappe remains the focal point, while Vinicius Jr provides another route into space.
Real also have the quality to change the game from the bench, something the 21-year-old Espi has already demonstrated since his summer arrival from Levante.