Atletico's Diego Simeone returns to cherished Milan for tough Inter battle
The Rojiblancos, fourth in LaLiga, need a strong run in Europe to make something significant of a season which started well but stalled with elimination in the Spanish Super Cup and Copa del Rey.
In their path lie the runaway Serie A leaders and last year's Champions League runners-up, with the first leg in Italy.
Simeone, who played for Inter between 1996-1999 winning the UEFA Cup in 1998, has fond memories from his time in Milan and has long been touted as a future coach of the Serie A side.
"Sooner or later, he'll end up at Inter," his sister and agent Natalia Simeone told newspaper La Gazzetta dello Sport in 2018.
"He loves the club, the atmosphere and living in Milan. Inter is a side he would really love to coach."
During the first half of last season it seemed Simeone was close to the end of his tenure in the Spanish capital, with Atletico struggling.
Rumours emerged suggesting Inter would move for the Argentine in the summer, but the state of play changed at both clubs before then.
Atletico bounced back strongly in the final months of the season and Simeone, encouraged greatly by the team's improvement, decided to extend his deal until 2027.
Meanwhile Simone Inzaghi's Inter found form and came within a whisker of winning the Champions League for the first time since 2010.
Atletico have never won it at all - and it is the one clear piece of unfinished business for Simeone, who has led the team to virtually every other trophy.
The coach steered them to the final in 2014 and 2016, only for rivals Real Madrid to defeat Atletico on both occasions in agonising fashion, in extra-time and on penalties respectively.
If Atletico are to break new ground this season, Simeone will have to lead them past his former - and potentially future - team.
Victory in Europe has become Atletico's key goal as they lie a long way off the pace in the Spanish title race.
Simeone rested Antoine Griezmann for the 5-0 win over Las Palmas on Saturday in LaLiga, indicating where his priorities lie.
"I'm sure he'll be annoyed because he didn't play, I thought he needed a pause," explained Simeone.
"We need a great Griezmann, and we need him fresh."
'Not just chance'
Simeone and Inzaghi both tend to line up with 3-5-2 formations and the matches promise to be an intriguing tactical battle.
Atletico's coach reserved special praise for Inzaghi, whom he played with at Lazio between 1999-2003.
"A team doesn't win the Super Cup or (lead) the league without being a very well-drilled side," said the Argentine.
"They have a coach, Simone, whom I have a good relationship with because I was with him at Lazio and he's doing very good things at Inter."
Inzaghi led Inter to last season's final, where they were narrowly beaten by Pep Guardiola's treble-winning Manchester City.
This year the Italians are head and shoulders above the rest domestically, suffering just a single defeat in the league, while they are unbeaten in Europe.
"They have only lost one game this season, they are strong, they believe in what they do, and do a lot of work both in defence and attack," Simeone told DAZN on Saturday.
"They got to the (Champions League) final last year and it's not just chance that they are leading Serie A."
Simeone, known for his manic touchline displays, sharp all-black suits and combative spirit, will not be as generous once the ball is rolling, Inter history or not.