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Simeone's team is looking for a win to continue in the Champions League, while the Londoners are relying on their home form and history against Spanish teams.
Arsenal enter the challenge against Atletico Madrid with a strong record at the Emirates, where they have lost only one of their last 24 European matches.
The Londoners have won 17 matches and drawn 6 in this series. Also this season in the Champions League, the team has won five of the six matches played at home.
Atletico Madrid face a clear task: they must win to advance. Diego Simeone's team is coming off a 2-0 win over Valencia in LaLiga, a result that has moved them closer to securing a place in the top four.
In Europe, the Spaniards have had a good run in semi-finals. Atletico have won six of the last seven European semi-finals, including their Europa League clash with Arsenal in 2018.
However, transfers remain the team's weakest point. Atletico have only won three of their last ten away games. They have lost three away games in the Champions League this season, all to English teams.
Their history in England doesn't help either. Atletico were beaten 4-0 at this stadium during the league stage and have lost six of their last seven visits to English soil.
Arsenal, meanwhile, are unbeaten in their last nine encounters with Spanish teams, with seven wins and two draws.
Bukayo Saka comes after a positive performance at the weekend, where he scored and provided an assist. For Atletico, Antoine Griezmann remains the main player in attack, especially after the break.
Julian Alvarez is expected to be absent for the Spanish team.
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