The hosts carry a 1-0 lead into Tuesday's last 16 second leg following Diego Costa's late header at the San Siro three weeks ago.
"They need to score, and, naturally, they will be playing attacking football," Simeone said of AC Milan. "Accordingly, our game will be different.
"We need to try to control the game. I think the key will be in the intensity that we put in midfield.
"If we can be strong then we can play the game we need.
"We need to be focused and careful not to give away many spaces as that would only benefit our rivals."
Atletico - who are second in La Liga, just three points adrift of leaders Real Madrid - have not reached the quarter-finals of Europe's elite club competition since 1997.
Milan, meanwhile, have won the European title seven times and Simeone, a former Inter Milan and Lazio player, knows the Rossoneri can never be underestimated.
"Milan are a strong club," he said. "They are accustomed to playing in this competition.
"I expect the best Milan and I'm sure we face a very hard game against a very difficult rival.
"They have great players."
Simeone sees AC Milan striker Mario Balotelli as the biggest threat to his team.
Balotelli returned to play at the weekend having missed Milan's last two league games with a shoulder injury.
Milan have endured a dismal domestic campaign and travel to the Vicente Calderon stadium on the back of Saturday's 1-0 loss at Udinese.
The outcome dropped the Rossoneri to 10th in the Serie A standings, 37 points behind runaway leaders Juventus.
"We have to think positive and be optimistic," AC Milan coach Clarence Seedorf said. "We need to convince ourselves that we can produce a great performance against Atletico.
"I have confidence in my team and I know my players will respond on the pitch."
Atletico defender Diego Godin, midfielder Arda Turan and striker Costa will return to the starting line-up having been rested for Saturday's 2-0 triumph at Celta Vigo.
Costa, who scored at the San Siro in the opening leg to hand his team the edge in the tie, will lead Atletico's attack.
AC Milan midfielders Andrea Poli and Nigel De Jong have made the trip to Spain but are doubtful for the encounter with minor injuries.