Schalke, meanwhile, simply have pride to play for having already been relegated.
Hoffenheim are not completely clear of relegation just yet, but with four teams and seven points between themselves and the relegation playoff position, any risk of them falling into the second tier of German football for the first time since 2008 looks slim.
Sebastian Hoeness has clearly made a conscious effort to tighten up the defence in recent weeks, with his side impressively keeping clean sheets against Bayer Leverkusen and RB Leipzig before overturning a 2-0 deficit to beat Borussia Monchengladbach 3-2.
Die Kraichgauer were less than 10 minutes of normal time away from keeping a third clean sheet in four matches last time out against Freiburg, but Vincenzo Grifo's late penalty cancelled out Andrej Kramaric's first-half strike to earn a share of the spoils.
Hoeness will certainly be targeting a win against struggling Schalke to all but secure safety for his side, while earning revenge for the 4-0 defeat to them in January.
Indeed, that victory was Schalke's first in the league for almost an entire calendar year, but it did not bring about the dramatic upturn in form which would have been required for them to mount an escape from relegation.
The club have changed manager since then, too, with Dimitrios Grammozis only winning one of his seven matches in charge so far.
Any hopes of him adding to that tally last time out against Arminia Bielefeld were significantly damaged by Malick Thiaw's 71st-minute red card after Fabian Klos had already provided the opposition with a narrow lead 21 minutes beforehand.
Schalke's 2020-21 season has undoubtedly been one of the worst for any team in Bundesliga history, with only Tasmania Berlin's tally of 10 points in the 1965-66 season worse than Schalke's 13 so far, although they still have time to improve on that of course.
Realistically, it is all about building for life in the second tier of German football now, with the recent signing of experienced second-tier striker Simon Terodde from Hamburger SV certainly reflective of that.
Whether Grammozis is handed the opportunity to be the man to take Schalke back to the top flight may depend on how his side fares in their final four matches of the season.
Hoffenheim's injury crisis shows little signs of easing up, with Hoeness sure to be hoping for much better luck on that front next campaign should he remain in charge.
Dennis Geiger, Ermin Bicakcic and Benjamin Hubner are all expected to miss the rest of the season, with Chris Richards and Stefan Posch facing a race against time to feature again in May having suffered hip injuries.
Hoffenheim possible starting lineup:
Baumann; Kaderabek, Vogt, Nordtveit, Sessegnon; Samassekou, Grillitsch; Skov, Kramaric, Adamyan; Bebou
Schalke 04 possible starting lineup:
Fahrmann; Aydin, Mustafi, Becker, Kolasinac; Serdar, Mascarell; Harit, Uth, Hoppe; Huntelaar
We say: Hoffenheim 3-1 Schalke 04
We expect Hoffenheim to put any lingering relegation concerns to bed with a win, although it may not come as easily as expected.
Both sides are missing several key defenders through injury and suspension, so the array of talented attackers on the pitch may well enjoy themselves.