The visitors, meanwhile, have already qualified for the knockout stages of European competition for the first time in the club's history, and would seal top spot in the group with a draw in Belgrade.
It has been an excellent campaign so far for the Serbian champions, who lead their domestic table by nine points after 16 matches and are all but through to the knockout stages of the Europa League.
Last week's 2-0 victory at Gent put Red Star, who competed in the Champions League group stage in the previous two seasons, six points clear of Slovan Liberec in Group L with only two matches remaining.
Given that they beat the Czech outfit 5-1 earlier in the campaign, it would take a catastrophic defeat on the final matchday against Slovan Liberec for Dejan Stankovic's side not to progress given that head-to-head separates sides level on points in European competitions.
The former Inter Milan midfielder will implore his side to put any doubts to bed by avoiding defeat against their forthcoming German opponents, however, with only a win keeping the 1991 European Cup winners' hopes of topping the group alive.
Hoffenheim, meanwhile, have failed to win any of their last seven domestic matches, but they have won all four Europa League games this season to qualify for the knockout stages with two matches to spare.
Having finished bottom of the group in their previous two European campaigns (one in the Europa League and one in the Champions League), it has been a remarkable turnaround for Sebastian Hoeness's side, who can secure top spot by avoiding defeat in Belgrade on Thursday.
Last week's 2-0 win at Slovan Liberec summed up their campaign thus far: controlled and clinical, with Christoph Baumgartner and Andrej Kramaric scoring late in the game for Hoffenheim having dominated possession throughout the match.
With qualification secured and their league form stuttering, Hoeness has the luxury of being able to rest players in his side's last two matches, but may look to secure top spot first.
Red Star Belgrade Europa League form: LWWW
Red Star Belgrade form (all competitions): WWWWWW
Hoffenheim Europa League form: WWWW
Hoffenheim form (all competitions): LWLDWD
The former Serbia midfielder is likely to deploy a back five in an attempt to contain the German side and gain the point his side needs to be certain of progression to the next round.
Dennis Geiger was sent off in the weekend's draw at Mainz 05 so should start given he is suspended for the next league match against Augsburg on Monday, while Sargis Adamyan (coronavirus), Kostas Stafylidis (shoulder), Ermin Bicakcic (knee) and captain Benjamin Hubner (muscular) will not make the trip to Belgrade.
Red Star Belgrade possible starting lineup:
Borjan; Gajic, Pankov, Milunovic, Degenek, Vukanovic; Nikolic, Petrovic, Ivanic; Falcinelli, Ben
Hoffenheim possible starting lineup:
Baumann; Bogarde, Kasim, Nordtveit, Skov; Rudy, Vogt, Geiger, Gacinovic; Beier, De Mello
We say: Red Star Belgrade 2-1 Hoffenheim
With Hoffenheim likely to rest several players and Red Star usually a tough trip for any side, we can see a narrow home victory here.
However, a draw would suit both teams, so it would be no surprise to see both sides settle for a point either should the game increasingly head in that direction.