Atlético Madrid begin their 2018/19 Champions League campaign with a tough away match against 2017/18 Ligue 1 runners-up Monaco on Tuesday.
Since the 2013/14 season, Simeone's side have reached the Champions League final on two occasions, as well as one semi-final appearance. However, last season's European venture did not exactly go to plan, with Atlético eliminated in the group stage for the first time in their Champions League history.
The side from Madrid have endured a tough start to this season's La Liga, sitting in eighth place after one loss and two draws, one of which came at home game against Eibar on Saturday. As a consequence of this poor form and Stefan Savić's red card in the second game of the season, Simeone has been forced to chop and change his side thus far this season.
Here's how the Argentinian manager might set up his team on Tuesday night.
1. Goalkeeper and Defenders
Jan Oblak (GK) - The Slovenian shot-stopper has been ever-present in Atlético's side this season and will almost undoubtedly start.
Juanfran (RB) - After the summer departure of Šime Vrsaljko to Inter Milan, Juanfran is now the undisputed starting right-back for Simeone's side. His tireless work-rate and defensive doggedness is representative of the Madrid side as a unit.
Diego Godín (CB) - The Uruguayan warrior is Atlético's captain and will again be leading his side out in Monaco on Tuesday. At his best he represents an immovable object in Madrid's defence.
José Giménez (CB) - Godín and his Uruguayan teammate have formed a formidable defensive partnership for club and country over the past few seasons. Whilst Giménez will face competition from Stefan Savić for this spot, the Montenegrin's recent red card against Celta Vigo means the Uruguayan centre-back has the edge.
Filipe Luís (LB) - The greatest competition for places in Atlético's lineup comes at left-back, with Brazilian international Filipe Luís battling it out with World Cup winner Lucas Hernández. So far this season, Filipe Luís has come out on top, starting in three of Atlético's four matches. Therefore, the Brazilian will be the favourite to start against Monaco.
Thomas Lemar (LM) - Atlético's £52.7m signing will be expected to start against his former club Monaco on Tuesday. Whilst there has been plenty of personnel changes in Simeone's midfield this season, the French international has started three of the four games thus far.
Saúl (CM) - The Spanish international burst onto the Champions League scene against Bayern Munich in 2016, scoring a sensational solo goal. Since that moment, there has been no looking back and Saúl is now a mainstay in both Atlético's team and Spain's.
Koke (CM) - Competition for places in the centre of midfield is high in Madrid's team, and Simeone has yet to settle on a suitable partner for Saúl this season. However, in two of the four La Liga matches this season, Koke has taken up this role. With Koke's vast Champions League experience, it seems likely that Simeone will opt for the Spaniard once more.
Ángel Correa (RM) - Having scored in Madrid's first match against Valencia, Correa has started in every game this season and seems to have earned the trust of Simeone.
Diego Costa (ST) - Diego Simeone, Atlético Madrid and Diego Costa are a match made in heaven. Since returning to the Spanish capital from Chelsea last summer, Costa has provided everything Simeone desires in a striker: strength, endeavour and a clinical eye for goal. Costa will be one of the first names on the team-sheet for Tuesday's match against Monaco.
Antoine Griezmann (ST) - After a stellar season last campaign, which saw the French striker play an instrumental role in winning both the Europa League and the World Cup, Griezmann has had somewhat of a tame start thus far. With only one goal in four games, Simeone will be hoping his star striker can regain his goal-scoring rhythm against Monaco.