Real have not won the domestic title since 2017 and have finished third in the last two seasons, results that have seen them cycle through three different managers and return to Zinedine Zidane.
But Barcelona's own domestic struggles have allowed Madrid to take a two-point lead at the top of the table, but now could face problems if injuries start to affect a squad already stretched in certain areas.
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Crucially, Los Blancos are 12 days away from a Clasico clash with Barca, the kind of fixture that will define their season and domestic campaign.
Playmaker Modric, a veteran in Madrid having arrived back in 2012, could not help his Croatia side overcome Wales as they drew 1-1 in Cardiff but more concerning for his employers was the nature of his departure from the game.
The former Spurs player was booked for a late challenge on Harry Wilson in the last minute of normal time but appeared to injure himself in the process.
A stretcher was called for but eventually not required, even though Modric had to be helped off the pitch by two members of Croatia's medical team.
One source inside the camp told Spanish outlet Radio Marca: "According to the doctors, Modric has received a painful blow to the quadriceps.
"It is logical that people are worried about the Clasico, but it does not seem likely [that he will miss it]."
It was a positive update but manager Zidane will remain concerned, especially after the Croatian returned from the last international break with leg injury that kept him out for more than two weeks.
But Madrid fans would have been even more worried seconds later when Modric's team-mate - but opposition on the night - Bale gestured to his own bench asking for treatment.
The 30-year-old appeared to have suffered a calf problem and while he was not substituted, the forward was clearly hampered and limped his way to the final whistle.
Manager Ryan Giggs tried to put supporters' mind at rest afterwards.
Bale was a passenger for the closing stages of the game
Image credit: Getty Images
"Gareth's just got a bit of cramp towards the end," Giggs told Sky Sports.
"He didn't want to come off, though.
"It was a fantastic performance from Gareth, it was just a shame that he did get that - it was about 10 minutes really at the end, so we were down one player really.
"But it looks like it's just cramp."