The three-time holders got their European campaign back on track with a 2-1 win against Plzen a fortnight ago, but they have since changed managers and are not yet assured of a place in the last 16.
The Czech champions are running out of time to make an impact in their third Champions League campaign, as they have yet to pick up a win from their three matches.
There is no shame in losing away to Real, though Plzen visited the Bernabeu at the perfect time for that clash two weeks ago and will perhaps be disappointed not to have nicked a point in the end.
Patrik Hrosovsky certainly made things interesting in the Spanish capital with his goal 11 minutes from time to set up a tense finale, but it proved nothing more than a consolation as Karim Benzema and Marcelo had already put Los Blancos two goals in front.
Viktoria held a two-goal lead of their own in their opening Group G outing, only to be pegged back in a 2-2 draw with CSKA Moscow on September 19, which they followed up with a chastening 5-0 reverse at the hands of Roma.
Time is therefore against Pavel Vrba's men, with a shock victory likely being needed at the Doosan Arena on Wednesday night if they are to have any hope of finishing in a top-two spot.
That is something they have not previously managed in the Champions League, finishing third in 2011-12 and again in 2013-14. Across those two previous European campaigns and the first half of this one, Viktoria have won one, drawn three and lost three of their seven home matches.
Vrba's side are winless in 10 Champions League matches overall, in fact, stretching back to a 2-1 qualifying win at Maccabi Tel Aviv in July 2015, and they have only one victory in seven attempts against Spanish opposition - a 1-0 home triumph over Atletico Madrid in the 2012-13 Europa League group stage.
Plzen are not exactly in the best of form heading into this latest tussle against La Liga opposition, either, as they have won just two of their last five matches in all competitions, though they did beat Banik Ostrava in their domestic league at the weekend to join Slavia Prague on 34 points at the top of the table.
Recent form in Champions League: DLL
Recent form (all competitions): WDLWLW
Since picking up a much-needed win in the reverse fixture against Viktoria on October 23, Real have sacked boss Julen Lopetegui and replaced him with Santiago Solari, who was previously in charge of the reserve side.
A heavy 5-1 loss to El Clasico rivals Barcelona five days later proved to be the final straw for the club's board, with that their fifth loss in seven matches.
Solari is now likely to be given the job until the end of the season, and the 42-year-old has made a positive start in his mission to steady the ship by earning wins against Melilla in the Copa del Rey and Real Valladolid in La Liga.
Anything other than a convincing win against lower-league side Melilla really would have been cause for concern, though the 2-0 success against Valladolid proved to be far more of a challenge, requiring a late own goal and a Sergio Ramos penalty to pick up a first league win in six attempts.
Even accounting for that victory at the weekend, Los Blancos can surely forget about challenging for the La Liga title this season, adding extra significance to the cup competitions.
Having lifted the European Cup in each of the last three seasons, and four times in the last five, Solari appears to be on a hiding to nothing. The rookie manager's first mission is to simply ensure that the champions avoid the embarrassment of dropping out of the competition in the group stage.
The 1-0 loss to CSKA Moscow on matchday two was just Madrid's fifth defeat in 35 European outings, but they responded with that 2-1 victory over Viktoria last time out, taking them to six points after also seeing off Roma 3-0 in their opening match.
Roma and Madrid are therefore in control of Group G, sitting on six points apiece - two better off than CSKA, who host the Giallorossi in an early kickoff on Wednesday, and five in front of Plzen.
Dropped points in this first of four successive away matches, however, and all of a sudden Real's hopes of reaching the semi-finals or better for a ninth year in a row will not look so clear.
Recent form in Champions League: WLW
Recent form (all competitions): LLWLWW
Vinicius Junior came off the bench to rescue Real in their 2-0 win against Valladolid on Saturday, possibly seeing him force his way into the starting lineup for the first time since joining.
Solari also has Isco pushing for inclusion on the left of his likely three-man attack, having gone with the disappointing Gareth Bale and Marco Asensio at the weekend, but he has fewer options at the other end of the field.
Raphael Varane, Marcelo, Dani Carvajal and Jesus Vallejo are all still sidelined, so Sergio Reguilon - Madrid's best player against Valladolid - should retain his place at left-back, with Nacho Fernandez required in the middle.
In terms of the hosts, they will be without Michal Krmencik for this fourth Group G outing as the forward injured his knee ligaments in the 2-1 defeat of Slovacko last week and is out for the rest of the season.
Viktoria Plzen possible starting lineup:
Kozacik; Reznik, Hejda, Hubnik, Limbersky; Hrosovsky, Prochazka; Havel, Cermak, Petrzela; Reznicek
Real Madrid possible starting lineup:
Navas; Odriozola, Nacho, Ramos, Reguilon; Modric, Casemiro, Kroos; Bale, Benzema, Vinicius
Head To Head
Last month's meeting at the Bernabeu marked the first time that these two sides had faced off in a competitive match.
This will be Madrid's first trip to the Czech Republic since a 3-2 win at Sparta Prague in November 2001 - their first away win in the country in five attempts.
The Czech champions' last home game against Spanish opponents, meanwhile, ended in a 3-3 draw against Villarreal in the 2015-16 Europa League group stage.
We say: Viktoria Plzen 0-2 Real Madrid
Madrid appear to have found their feet since Solari replaced Lopetegui, with back-to-back victories giving them some momentum ahead of a tough run of fixtures away from home. The 13-time European champions may have lost at CSKA in their most recent European away game, but that was just a fourth defeat in 19 games on the continent and they should have few problems at the Doosan Arena.