Seeking a place in the quarter-finals for the first time since 1997, when Simeone was an Atletico player, Madrid's second club lead the seven-times European champions thanks to Diego Costa's header seven minutes from time in last month's first leg at the San Siro.
Simeone told a news conference previewing the return at the Calderon Milan would be forced to go on the attack as they try to avoid a trio of exits in Spain following defeats to Barcelona in the last eight in 2011-12 and the last 16 last season.
"We have to contain and control the game," Simeone said.
"The clash will depend on the intensity we produce in the midfield," added the Argentine, who had playing stints with Milan's city rivals Inter and fellow Serie A side Lazio.
"An open game will better suit Milan. They are an attacking team given the characteristics of their players. We need to make the most of the space they give us."
Simeone said he expected a tough test for his players even though Milan are struggling in their domestic league.
Clarence Seedorf was brought in to replace the sacked Massimiliano Allegri as coach in January but the former Milan, Real Madrid and Netherlands midfielder has yet to revive the club's fortunes and they are mired in mid-table and in serious danger of missing out on a European qualification berth.
"It is a very powerful institution," said Simeone, who was well acquainted with Seedorf, six years his junior, from their shared time in Italy and Spain as players.
"They are used to this competition and they have players with a lot of talent.
"I expect the best version of Milan. It will be a difficult game because there is a lot at stake. And that is when the great players step up irrespective of their current situation."
- Sports & Recreation