The Swiss side are well-placed to extend their campaign into the knockout phase too, but must avoid defeat in order to prevent Cluj potentially climbing back into the reckoning for a top-two spot.
The home side are already on 10 points - three more than Young Boys - and will win the group if they avoid defeat against the Swiss champions, who can also ensure further progress if they achieve a better result at the Olimpico than CFR manage at home to eliminated CSKA Sofia.
Even if results go against them on Thursday, Gerardo Seoane's team host their Romanian rivals next week and can still seal safe passage to next year's knockout rounds then.
In the reverse fixture, Roma came from behind to defeat Young Boys 2-1 in Berne on the opening night, with first European goals from Bruno Peres and Marash Kumbulla. After Jean-Pierre Nsame's early penalty proved not enough, YB suffered their first ever defeat by Italian opposition in Berne, having won their previous three ties against teams from the peninsula.
More often to be found at Champions League level, the Giallorossi have now secured four qualifications from as many Europa League group stage campaigns. Coach Paulo Fonseca may therefore take the opportunity to rest some legs with a recent defensive injury crisis still not fully resolved and a challenging encounter with Serie A surprise package Sassuolo on the agenda this Sunday.
Last week their emotionally-charged visit to Napoli ended in a chastening 4-0 defeat. Goalkeeper Antonio Mirante had a 90-minute nightmare and returning striker Edin Dzeko looked well off the pace following his recent COVID-19 infection, as Fonseca's side lost in Serie A for the first time since July.
Young Boys are competing for the seventh time in this competition's group stage, from which they have only made further progress twice before - in 2010-11 and 2014-15 - but not in their three most recent campaigns.
The Berne club's win in Sofia last time out was only the second they have managed in their last 24 European away games, losing 14. Though a difficult proposition for any side when at home, their record on the road in the Europa League proper reads W3 D8 L11.
That is slowly improving though, with no defeats in their last four matches. The 1-1 draw in Cluj last month was YB's third in a row with that scoreline before victory in Sofia.
Gerardo Seoane's side have scored in each of their last six Europa League away games too, so they can travel to the Italian capital in expectation, not just in hope.
Sunday's comfortable 3-0 win at Lausanne left them two points clear at the top of the Swiss Super League, which they are seeking to win for the fourth time in a row. Seoane even took the opportunity to rest chief goal threat Nsame, who will be keen to add to his strike in the reverse fixture against Roma - but this time in a winning cause.
Roma Europa League form: WDWW
Roma form (all competitions): WWWWWL
Young Boys Europa League form: LDWW
Young Boys form (all competitions): DWDWWW
Having already qualified for the knockout phase, Roma coach Paulo Fonseca is likely to field a shadow side.
Chris Smalling is struggling with a knee injury, while fellow defender Federico Fazio is in quarantine. Fortunately, Marash Kumbulla registered a negative virus test earlier in the week and can provide cover for the never-ending conveyor belt of absences in the Roma back line.
Young Boys saw skipper Fabian Lustenberger succumb to a back injury against CSKA Sofia last week, so the experienced defender will be unavailable for the trip to Italy. Long-term absentees Marvin Spielmann and Sandro Lauper remain out of action.
Tactically-flexible coach Gerardo Seoane generally employs a variation on 4-4-2 but could potentially return to the 3-4-3 he used in the reverse fixture in order to combat the opposition's usual 3-4-2-1 formation, with young wildcard Felix Mambimbi ready to impress if given the chance.
Roma possible starting lineup:
Lopez; Kumbulla, Cristante, Jesus; Peres, Milanese, Villar, Calafiori; Pellegrini, Perez; Mayoral
Young Boys possible starting lineup:
Von Ballmoos; Hefti, Camara, Burgy, Garcia; Fassnacht, Rieder, Sierro, Sulejmani; Mambimbi, Nsame
We say: Roma 2-2 Young Boys
After a crushing league defeat at the weekend, Roma boss Fonseca may welcome the opportunity to refresh his starting XI - particularly in the knowledge that Europa League progress is already assured.
Nonetheless, his young charges - full of potential and verve - are still capable of holding Swiss champions Young Boys, whose own qualification hopes may well go down to the last day.