With title rivals Barcelona and Real Madrid facing off at the Bernabeu later in the day, three points would see Atletico match their city rivals on points prior to the Clasico kick-off.
While Real Betis are clear bottom of the Spanish top flight, they have gone three league games unbeaten as their fight for survival intensifies.
And Simeone was all too aware of Betis' quality, despite the fact they sit nine points deep in the relegation zone.
"I expect to face a Real Betis team that has grown a lot under Gabriel Calderon's charge," Simeone said on Saturday.
"They've competed very well in their recent games. They surely suffered a tough blow last Thursday against Sevilla (in the UEFA Europa League).
"But they have improved in La Liga and that is what I look at. They have balance in midfield as well as toughness and intensity. So we obviously have to play the way we have until now.
"We hope to respond in the best way possible going into this hard fixture because of the rival's necessities. For them it's a must-win game. So it is for us.
"It'll be a game with benefits for both teams at stake. The aims are obviously different for each side."
Simeone's men are preparing for the ominous task of tackling Barcelona in their two-legged UEFA Champions League quarter-final starting in April but the Atletico boss was simply pleased to know at least one of his countrymen will be going to the final four.
"We'll face a Barcelona team that have reached the last six semi-finals of the UEFA Champions League. We are talking about the best," he said.
"On the other hand, I'm happy as an Argentine for the fact that there will be at least one Argentine manager in the semis. I'm sure this is good news for Tata Martino and also for me."
