The hosts, meanwhile, may require four points from their final two matches to avoid finishing in the bottom three.
Match preview
Indeed, after moving away from the relegation zone by winning three consecutive matches either side of the most recent international break, three defeats from their last four matches have drawn Hoffenheim back into trouble.
Pellegrino Matarazzo's side were edged out by Wolfsburg in a 2-1 defeat last time out, with Joshua Guilavogui's own goal in injury-time ultimately arriving too late for Die Kraichgauer to be able to mount a creditable comeback.
With a final day trip to their relegation rivals Stuttgart ahead of them, Hoffenheim will be desperate to gain a positive result against Union Berlin on Saturday to ensure that their destiny remains in their own hands regardless of results elsewhere.
Both Stuttgart and Schalke 04 head into the weekend within three points of Hoffenheim from the automatic relegation and relegation play-off spots respectively, so defeat for Matarazzo's side could prove disastrous ahead of their final day showdown.
On the flipside, victory for Union Berlin would all but ensure that they carry off one of the most remarkable overachievements in European football in recent years by qualifying for the Champions League.
Urs Fischer's side appeared to be stuttering having won only one of their previous six matches ahead of their trip to Freiburg last weekend, but they delivered against their rivals when it mattered most in the form of a sensational 4-2 victory.
A brace from Sheraldo Becker trebled Die Eisernen's half-time lead after Kevin Behrens had opened the scoring after only five minutes, but nerves at Stadion An der Alten Forsterei were jangling when the visitors pulled two goals back through Manuel Gulde and Vincenzo Grifo.
An equaliser for Freiburg would have meant them remaining level on points with Union Berlin in fourth spot heading into the final two matches of the season, but instead Aissa Laidouni's late strike helped his side move three points clear of their opponents with a significantly stronger goal difference to boot.
As such, one win from their last two games should prove enough to secure a top four position, although Fischer's side require four points to be mathematically certain of matters.
With a final day match against Werder Bremen at home still to come, avoiding defeat against Hoffenheim may be viewed as a positive result this weekend, although the outcome of Freiburg's match against Wolfsburg on Friday night will undeniably have a huge baring on matters.
Hoffenheim Bundesliga form:
W
D
L
L
W
L
Union Berlin Bundesliga form:
L
D
W
D
L
W
Team News
Hoffenheim will remain without Stanley Nsoki for one more match after the defender's recent dismissal against Eintracht Frankfurt, with fellow defenders Kevin Vogt and Pavel Kaderabek both ruled out for the season due to leg injuries.
However, Dennis Geiger returned to the matchday squad last time out following a back issue, with Matarazzo likely to be considering making a couple of changes after his side's disappointing defeat to Wolfsburg.
Robert Skov could come into the starting XI in order to provide more solidity at wing-back, with Ihlas Bebou potentially moving up front in place of Munas Dabbur.
Union Berlin, meanwhile, may have to replace Diogo Leite due to a head injury, with Paul Jaeckel the most likely candidate to come into the visitors' defence should Fischer persist with a back three.
Otherwise, Fischer is unlikely to make any changes to a winning formula, with the likes of Laidouni, Jordan Siebatcheu and Niko Giesselmann potentially having to make do with making an impact from the bench.
Hoffenheim possible starting lineup:
Baumann; Kabak, Brooks, Akpoguma; Skov, Rudy, Promel, Angelino; Kramaric, Baumgartner; Bebou
Union Berlin possible starting lineup:
Ronnow; Doekhi, Knoche, Jaeckel; Trimmel, Schafer, Khedira, Haberer, Roussillon; Becker, Behrens
We say: Hoffenheim 2-2 Union Berlin
This is a hugely important match for both teams at either end of the table, with a victory potentially enough for either side to achieve their respective ambitions.
However, avoiding defeat would not be the end of the world as it would ensure that their destiny remains in their own hands heading into the final match of the season, or potentially even better than that depending on results elsewhere. As such, we can envisage a share of the spoils after an entertaining affair.