Diego Costa's goal in San Siro earned Atletico a 1-0 advantage from the first leg, but Simeone knows the job is far from over.
Milan have had an indifferent season in Serie A, but the Argentinian remains wary of the threat posed by Clarence Seedorf's men.
"I'm sure we'll have a tough, tough games because there's a lot at stake," he said.
"The resolution of the game will be in control in the middle of the field.
"The opponent has great players and we have to expect the best from Milan."
Defender Diego Godin echoed the sentiments of his manager, warning against complacency.
"We have a slight advantage but we cannot trust that, you have to play like a final," he said.
"We look forward to the Champions League. I hope we can grow further as a group and in football."
