Düsseldorf manager Uwe Rosler looked on angrily after his side threw away a 2-0 lead against Rhineland rivals Köln on Sunday, with the relegation-threatened side shipping two late goals to draw for the fourth consecutive game.
A day earlier, David Wagner's Schalke continued their post-lockdown slump with a limp 3-0 defeat against lowly Augsburg - meaning they have taken just one point from their last five matches in the Bundesliga.
Both managers will be looking to this clash as a way of revitalising their campaigns, especially with both sides still embroiled in purposeful battles at both ends of the table.
Düsseldorf sit just three points adrift of guaranteed top-flight football next season, with Werder Bremen's Saturday win against Freiburg increasing the pressure on Rosler - who joined the strugglers in January.
Despite their terrible recent form, Schalke are only outside of the European football places on goal difference - but will be alarmed by the impressive recent displays by Hertha Berlin, Borussia Mönchengladbach and Wolfsburg.
The reverse fixture produced a scintillating 3-3 draw at the VELTINS-Arena, with Düsseldorf's Rouwen Hennings netting a late strike to seal his hat-trick. Schalke emerged 2-0 victors at the Murker-Spiel Arena last season.
Manchester City loanee Zach Steffen remains sidelined for the hosts, with the American suffering from a chronic knee problem for the entirety of 2020 so far.
However, Turkish defender Kaan Ayhan looks set to be handed a return to the side after his yellow-card suspension - with former Huddersfield man Mathias Jørgensen to make way.
Schalke boss Wagner has a wealth of injury worries to manage, with Amine Harit, Jean-Clair Todibo and top scorer Suat Serdar all set to miss Wednesday's fixture - with the latter limping out of Saturday's humbling loss in Gelsenkirchen. Ex-Fortuna man Benito Raman is set to lead the line with Michael Gregoritsch.
The visitors could be boosted by the returns of Benjamin Stambouli and Ozan Kabak.
Fortuna Dusseldorf (3-5-2): Kastenmeier; Ayhan, Hoffmann, Gießelmann; Zimmermann, Stöger, Morales, Thommy, Suttner; Karaman, Hennings (C).
Schalke (4-3-1-2): Schubert; Kenny, Sane, Nastasic, Oczipka C); Caligiuri, McKennie, Schöpf, Matondo; Gregoritsch, Raman.
Salif Sane vs Rowen Hennings
Wednesday's clash may dredge up bad memories for Schalke, who were run ragged in November by Hennings - with the nomadic German scoring his first-ever Bundesliga hattrick in a 3-3 draw.
Schalke's rearguard that day was missing the formidable presence of Salif Sane, who was absent with a serious knee injury. Sane's return to the side has seen some questionable results, with the Senegalese international coming under fire for his performances in both defeats since the return of Bundesliga action.
32-year-old Hennings has netted 11 league goals this season for Fortuna in their bid to secure top-flight football for next season. Will Sane be able to banish the ghosts of Schalke's past and keep Hennings' goalscoring guile at bay?
Benito Raman & Michael Gregoritsch vs Kaan Ayhaan
Schalke have been misfiring of late, having scored just twice in their nine-game winless run. A factor that could heighten this problem is the absence of top scorer Suat Serdar and deputy marksman Amine Harit, who have contributed 13 goals between them in the Bundesliga this season.
Standing in for Schalke's sidelined stars is Benito Raman and Austria international Michael Gregoritsch - who have netted just five combined efforts. Raman's pace could prove vital for Schalke in exposing Fortuna's defensive frailties, possibly making headway for Gregoritsch to capitalise on his aerial prowess.
Tasked with preventing this newly-forged partnership will be Fortuna's returning Ayhaan, who comes back into the side after serving a one-match ban.
How and where to watch
Wednesday's game will be available to watch in the UK on BT Sport 1, with coverage starting after the conclusion of RB Leipzig vs Hertha Berlin. Streaming is also available via the BT Sport App or the BT Sport website. Kick-off is at 19:30 BST.