The Giallorossi arrive on the back of four wins in a row - with 13 goals scored and just one conceded in the process - while hosts Cluj were battered by the same opponents last time out in Europe and have lost their last two home matches in the league.
Having beaten Cluj comprehensively at the Stadio Olimpico to move clear at the top of Group A, Roma should go into this week's reverse fixture against the Romanian champions bursting with confidence.
Paulo Fonseca's side took an early lead against the Railwaymen earlier this month - through chief chance-maker Henrikh Mkhitaryan's header - and eventually cruised to a comfortable 5-0 win, which was their biggest in the Europa League. Spanish striker Borja Mayoral also contributed a double while standing in for self-isolating star striker Edin Dzeko to leave Roma in a strong position to progress.
Roma's 2-1 win at Young Boys on the first matchday was only their second victory in their last eight European matches outside Rome, losing four. Their overall away record in the UEFA Europa League group stage, however, is W4 D4 L2, with wins in the two most recent fixtures.
Precedent will be in their favour this week, as the Italian giants have never lost in Romania - though three of their four matches in the country have been draws, two of them goalless. Their only win there came in a 3-1 success against Cluj some 12 years ago.
At the weekend, Roma benefited from another Mkhitaryan masterclass as the Armenian wizard produced two more spectacular strikes to brush helpless Parma aside in Serie A. In the absence of Dzeko, the ex-Borussia Dortmund star has risen further to the fore and clearly shrugged off several years of under-performance.
With their chief tormentor from the Olimpico mauling firing on all cylinders and Bosnia striker Dzeko now back in the Roma squad, Cluj may be fearing a repeat performance at home.
That heavy loss was their first defeat in the group though, still leaving them level with Swiss side Young Boys on four points – with three fewer than Roma and three more than fourth-placed CSKA Sofia.
Penalty shoot-outs aside, Cluj are unbeaten in their last seven European home games too, winning four. They won all three in last season's Europa League group stage - against Lazio, Rennes and Celtic - before drawing 1-1 against Young Boys in this season's second group fixture.
A loss at home to UTA Arad on Sunday undermined preparations somewhat, as a more offensive 4-3-3 lineup could not force the win needed to catch up with Liga leaders FCSB (formerly Steaua Bucharest, now controversially renamed). An increasingly inconsistent start to the campaign sees them sitting in third place, six points adrift of their fierce rivals from the Romanian capital.
Ex-Genoa and Chelsea full-back Dan Petrescu, in his second spell as CFR's manager since March 2019, had caused consternation with his comments in the aftermath of their loss in Italy three weeks ago, reportedly claiming that he was going to resign straight after the game.
The Italian press quoted the itinerant coach as declaring: "I want a break, I can't take it anymore. I need a rest," but Petrescu remains in situ for now.
Recent results, the upcoming visit of Paulo Fonseca's relentless side and now a COVID-19 outbreak amid his squad will hardly have improved his maudlin mood. How he handles such adversity could well define his club's prospects of remaining in Europe until the new year - and whether they can hold back the Roman hordes on Thursday night.
CFR Cluj Europa League form: WDL
CFR Cluj form (all competitions): WDLLWL
Roma Europa League form: WDW
Roma form (all competitions): DDWWWW
Returning Roma striker Edin Dzeko is one game away from his 100th appearance in UEFA club competition - scoring 41 goals in his 99 European matches to date - and has been passed fit to return from his spell in quarantine. Borja Mayoral, who has fared well in his absence, would make way if Paulo Fonseca decides to bring his main man back in at the earliest available opportunity.
CFR Cluj possible starting lineup:
Balgradean; Susic, Manea, Ciobotariu, Camora; Soares, Chipciu, Itu, Dokovic; Debeljuh, Rondon
Roma possible starting lineup:
Lopez; Jesus, Smalling, Ibanez; Peres, Diawara, Villar, Spinazzola; Pellegrini, Mkhitaryan; Mayoral
We say: CFR Cluj 1-3 Roma
A re-run of early November's Roman horror show is a very real prospect, given the respective form of either side.
Roma, however, have defensive concerns due to injury and infection, so will be more than happy to come away with three straightforward points from their Transylvanian trip. Returning hero Edin Dzeko can help seal the win needed to effectively seal onward progress.