Only victory can help Roma secure a direct route to the Europa League's last 16, as they host Sheriff Tiraspol in Thursday's Group G finale.
To avoid a playoff, the Giallorossi must win at Stadio Olimpico and hope Slavia Prague slip up against Servette; meanwhile, their visitors have already been eliminated and will finish last no matter what happens in Rome.
Match preview
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Having been held to a 1-1 draw by Servette last month, when Romelu Lukaku's first-half strike was not enough to seal three points against the Swiss side in Geneva, Roma's Group G fate is out of their hands heading into the final matchday.
Although a place in the Europa League knockout phase has already been assured, thanks to three wins from four previously, Jose Mourinho's men will face a playoff against one of eight third-placed finishers from the Champions League's group stage if they cannot leapfrog Slavia Prague, who lead the table by two points.
As Slavia also have a superior goal difference, even one more point could see the Czech club through on Thursday evening - providing Roma do not beat Sheriff by at least four goals.
The Giallorossi both won and lost 2-0 against their rivals for top spot earlier in the process, in addition to taking four points from Servette, and after winning 2-1 in Transnistria when they last met Sheriff - with Lukaku on target again - the Serie A side will now aim to wrap things up with another success.
Last weekend, Roma welcomed Fiorentina to the Italian capital on the back of three wins from four league matches, and despite losing both Nicola Zalewski and opening goalscorer Lukaku to red cards during a tempestuous finale, they grimly held out for a 1-1 draw.
That result kept Mourinho and co inside Serie A's top four on goal difference - with a trip to fifth-placed Bologna scheduled for this Sunday - but last season's beaten finalists now turn their thoughts to the Europa League.
While Roma plan to be back in the final next year, Sheriff's latest European adventure is already coming to an end, as they cannot even catch third-placed Servette in the Group G standings, after taking just one point from five games so far.
It took a last-gasp penalty from Slavia Prague's Muhamed Tijani to deny the Moldovan club a 2-2 draw last time out, and another loss left any lingering hopes of snatching a Conference League playoff place dead in the water.
After exiting the Champions League preliminaries to Maccabi Haifa, Sheriff came through Europa League qualifying to make their sixth group stage appearance in UEFA's second-tier tournament, but as on every other occasion they have again failed to reach the last 16.
By contrast with their continental results, Roman Pylypchuk's side sit top of Moldova's National Division with 14 wins from 17 matches, but they did concede three goals again in their most recent outing - a shock 3-1 defeat to FC Balti.
Team News
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With a crucial league clash against Bologna set for Sunday - and having completed last week's game with nine men - Jose Mourinho is likely to make several changes to his starting lineup on Thursday evening.
Zeki Celik, Edoardo Bove, Andrea Belotti and back-up goalkeeper Mile Svilar are all strong contenders for promotion from the bench, as Mourinho rotates his resources.
Suspensions for Nicola Zalewski and Europa League specialist Romelu Lukaku (24 goals in 38 matches) only apply to Serie A, so both could be retained - particularly as Lukaku's attacking colleagues Paulo Dybala and Sardar Azmoun both picked up injuries against Fiorentina. However, Ivorian defender Evan N'Dicka must serve a one-match European ban.
Tammy Abraham and Marash Kumbulla remain on the road to recovery from ACL injuries, with the latter now finally nearing his return, while defensive duo Chris Smalling and Gianluca Mancini are also sidelined.
Sheriff, meanwhile, will have Gaby Kiki and Armel Zohouri back in the fold, after they were both suspended against Slavia Prague for receiving red cards in a dramatic late defeat to Servette, but Peter Ademo and Rasheed Akanbi are ruled out by injury.
Recently linked with a move to FCSB in Romania, David Ankeye - on loan from Tunisian side Hammam Sousse until the end of the season - has scored eight goals and provided two assists so far this term. The Nigerian striker should start up front at Stadio Olimpico, with support from Henrique Luvannor or Ricardinho.
Roma possible starting lineup:
Svilar; Celik, Cristante, Llorente; Karsdorp, Bove, Paredes, Aouar, Zalewski; Belotti, Lukaku
Sheriff Tiraspol possible starting lineup:
Koval; Zohouri, Tovar, Kiki; Mbekeli, Badolo, Talal, Fernandes, Artunduaga; Ricardinho; Ankeye
We say: Roma 2-1 Sheriff Tiraspol
Roma have recently been dominant on home soil, winning five games on the spin as hosts before drawing with Fiorentina last time out. With some high-calibre options among his fringe players, Jose Mourinho can still send out a side that sees off Sheriff - but a win for Group G leaders Slavia Prague may still consign them to the playoffs.
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