The match at fourth-placed Bilbao's daunting San Mames arena was seen as one of Atletico Madrid's toughest of the season finale and failure would have severely dented their chances of beating Barcelona and Real Madrid to the title.
As part of their preparations for the crunch game in the Basque Country, Simeone decided to call in some outside help and invited a woman to speak to the players at the team hotel a few hours before kick-off who knows from the bitterest personal experience what it takes to triumph in adversity.
Irene Villa and her mother Maria, who worked for the Spanish police, were driving to school in Madrid in October 1991 when a bomb planted by Basque separatist group ETA exploded under their car. Irene, then aged 12, lost both her legs and three fingers of one hand and her mother a leg and an arm.
Now 35, married to Simeone's Argentine compatriot Juan Pablo Lauro and mother to an infant son, Irene has recovered from the trauma of the attack to carve out a successful career as a life coach and journalist.
She is also a Spanish para-alpine skiing champion and successful author whose latest book "It's never too late, princess" tells the story of six characters dealing with challenges such as disability, drug addiction and cancer.
"Simeone wanted to continue transmitting strength, motivation and dedication to his team," Villa said in an interview with Reuters as Atletico Madrid prepare to host Chelsea in the Champions League semi-finals on Tuesday.
"I think my story and my message were able to achieve all that," she added, describing herself as "happy, extrovert and someone who enjoys life to the full".
"It was an extra push for a team which is showing that there are no limits and that they know it can be done."
Villa said she tried to communicate in her 40-minute presentation the importance of fighting, never giving up and having the confidence to know you can be the best.
"I told them the story of my (skiing) team ... of the difficulties of all kinds that we encountered at the start.
"And how after serious injuries and tumbles but with a lot of determination, training and preparation we achieved podium finishes even outside Spain.
"The reaction (of the Atletico Madrid players) was incredible. Their faces spoke volumes.
"A silence like the grave and then hugs and congratulations. They went away amazed."
After leaving the hotel and heading across town to Bilbao's stadium, where Barcelona lost 1-0 and Real Madrid could only manage a 1-1 draw this season, Atletico Madrid fell behind in the sixth minute but hit back through top scorer Diego Costa in the 22nd.
Midfielder Koke struck the winner 10 minutes into the second half and Atletico Madrid have won their subsequent three matches, putting them in a strong position to claim their first La Liga title since 1996 when a team featuring Simeone in midfield won a domestic league and Cup double.
"The match was very emotional, one of the best of the season," Villa said.
"They were unbeatable! It is very motivating although of course the merit is all for Simeone and his players."
Few would have given Atletico Madrid the remotest chance of challenging wealthy Real and Barca for the La Liga title this season but Simeone has turned his unfancied squad into genuine contenders in Spain and Europe.
He told reporters recently he had asked Villa to speak to the players and coaching staff because her values were very similar to his own.
"We invited her simply so that she could tell us the story of her life, so we could see the realities," he said.
"It really did us a tremendous amount of good, we felt very comfortable and we have one more friend now at Atletico Madrid."
Atletico Madrid's Brazil left back Filipe Luis, who tweeted a picture of himself holding Villa's book this month, said it had been a long time since anything had affected him emotionally quite as much.
"Personally I have been through difficult situations that are not even a tenth of what this fighter has been through," he said.
"You can look at life in two ways. And the example she gives of looking at it positively and optimistically is incredible."
Atletico Madrid will be assured of the La Liga title if they win three of their remaining four matches and are within touching distance of a first European crown.
If they pull off what would be a stunning achievement in either competition, one person they will be toasting at the traditional celebrations in central Madrid will be the inspirational Irene Villa.