The newly-crowned kings of Spain could complete an incredible double should they beat their city rivals in Lisbon, though they may be without their star strikerAtletico Madrid stand on the brink of an unlikely double as they prepare to take on city rivals Real Madrid in the Champions League final.
Few would have predicted Atleti's first Liga title since 1996 at the beginning of the season, but Diego Simeone's men made sure of the trophy with a 1-1 draw against eventual runners-up Barcelona at Camp Nou on Saturday.
And the Vicente Calderon outfit have backed that up with equally impressive displays in Europe's elite club competition, beating Chelsea in the semi-finals to reach the Lisbon showpiece, while Real overcame defending champions Bayern Munich in emphatic fashion.
However, talk in the build-up to this weekend's mouthwatering Madrid derby has been dominated by the fitness and availability of both clubs' star names.
Diego Costa was left in tears after suffering a hamstring strain in the draw at Barca, and has reportedly travelled to Serbia for specialist treatment on the injury - a desperate bid to be in contention for the biggest match of his career.
As the joint-third top goalscorer in the competition, Costa's absence would come as a huge blow to Atleti, especially as the tournament's leading marksman Cristiano Ronaldo has been cleared to play for their opponents.
The Portuguese has been the star of Real's run to the Estadio da Luz showdown, scoring 16 goals in Europe this season, but missed his side's last two games because of a muscle injury sustained in a 1-1 draw at Real Valladolid earlier this month.
Despite the Costa setback, Simeone is confident his players are prepared for the challenge that lies ahead.
"It's a historic rivalry. It's great, both in terms of the matches themselves and the fact that in one city you have such a powerful team as Real Madrid and a battling team such as Atletico Madrid.
"Each team uses the tools it has at its disposal and it's a great rivalry, no matter which team you support."
Real are going in search of a 10th title in top-level European competition and Ronaldo knows the pressure is on to deliver La Decima to the supporters.
"It is a moment that all Madridistas are dreaming about - the decima," he said. "We are all very excited, so we have to win.
"It will be a special game. I will be playing in my home country."
This will be the first meeting between two teams from the same city in the history of European Cup and Champions League finals, and the duo from the Spanish capital have only met on one previous occasion in continental competition.
Atleti edged the league encounters between the sides this season - winning 1-0 at Santiago Bernabeu before a 2-2 draw on home soil - but Real claimed a 5-0 aggregate win when they met over two legs in the Copa del Rey semi-finals.
Real boss Carlo Ancelotti will be forced to make do without the suspended Xabi Alonso, while Karim Benzema (hamstring) and Pepe (calf) are doubtful.
As well as Costa, Atleti - unbeaten in the tournament so far - have question marks over the fitness of Arda Turan (knee).