With a perfect record so far, the visitors arrive in the Eternal City leading their hosts by three points in the standings, while both are faring well domestically.
Match preview
Beaten on the opening day of the Europa League group stage, Roma lost to Bulgarian champions Ludogorets at the start of September, but then bounced back with a victory over HJK Helsinki last time out.
Aided by the Finnish side's captain Miro Tenho receiving a red card after just 14 minutes, Jose Mourinho's men swept their short-handed opponents aside - firing in 29 shots on goal in a comfortable 3-0 home win.
Roma went all the way in the inaugural Europa Conference League last season and lifted the trophy in Tirana, and as an ambitious outfit are eager to emulate that feat in Europe's second-tier tournament. Their fate, though, rests heavily on events during the next few days.
Set to meet Real Betis twice in short order, with the return fixture in Seville scheduled a week after Thursday's encounter at the Olimpico, the Giallorossi cannot afford to slip up - particularly as Ludogorets may well take maximum points from their double-header with HJK.
Now hosting their Spanish counterparts for the first time ever in a competitive game, Roma have gone unbeaten throughout their last 20 home matches in Europe; winning 14 times in the process.
Though they actually suffered a rare setback on Roman soil last time they played host in Serie A - losing 1-0 to Atalanta - Mourinho subsequently led his side to an ever more scarce away victory over fellow top-six contenders.
Winning against his old club Inter at San Siro at the weekend - while watching on from the club bus due to a touchline suspension - will have reaffirmed that Roma are heading in the right direction under his leadership and also boosted morale in the camp.
While goals from the irrepressible Paulo Dybala and defensive mainstay Chris Smalling earned Roma three points on Saturday, less than 24 hours later, Real Betis were beaten for only the second time this term.
Having had former Lazio defender Luiz Felipe dismissed early in the game - when they were already one goal down - Los Verdiblancos succumbed to Celta Vigo; leaving them fourth in La Liga.
Nonetheless, they have won seven of their nine matches in the 2022-23 campaign to date, with the only other defeat coming away to defending champions Real Madrid - a former club of their veteran coach Manuel Pellegrini.
After seeing off HJK in their first Europa League fixture, Betis were pushed closer by Ludogorets last time out; ultimately winning 3-2 at Benito Villamarin. They therefore sit at the summit of Group C, and can exert a stranglehold on its leadership should they come out on top in their tussles with Roma.
Lifting the Copa Del Rey in April brought about a feel-good factor similar to that enjoyed by their Conference League-winning opponents, and as both sides continue their search for more silverware, a fascinating duel will be fought in the coming days.
Roma Europa League form:
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Roma form (all competitions):
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Real Betis Europa League form:
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Real Betis form (all competitions):
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Team News
Set to host Lecce at the weekend, Roma will once again refresh their starting XI on Thursday, as they continue to fight on two fronts.
Rui Patricio should step aside for cup goalkeeper Mile Svilar, while Andrea Belotti may start up front after scoring his first Europa League goal against HJK last time out in Group C.
Having battled through the clash with Inter, captain Lorenzo Pellegrini is likely to miss out due to an ongoing muscular problem, and Dutch pair Georginio Wijnaldum and Rick Karsdorp remain long-term absentees. However, Marash Kumbulla and Stephan El Shaarawy were back at Jose Mourinho's disposal on Saturday, and both are likely to be involved after being consigned to the bench in Milan.
While Betis forward Juanmi is out of action until after the World Cup due to an ankle injury, chief creator Nabil Fekir could now return to the starting side after a spell on the sidelines.
After making his comeback as a substitute in Vigo, the French midfielder may be ready to support lone striker Borja Iglesias, who has scored six La Liga goals so far this term. Willian Jose is an alternative option for Manuel Pellegrini to consider up front, having found the net twice already in the Europa League.
Forty-one-year-old skipper Joaquin is set for selection on the wing, as he closes in on a century of career appearances in European competition - he currently stands four games short.
Roma possible starting lineup:
Svilar; Mancini, Ibanez, Kumbulla; Celik, Cristante, Matic, Spinazzola; Zaniolo; Belotti, Abraham
Real Betis possible starting lineup:
Bravo; Montoya, Pezzella, Felipe, Moreno; Rodriguez, Carvalho; Henrique, Canales, Joaquin; Iglesias
We say: Roma 2-2 Real Betis
Made of sterner stuff on home soil, Roma can hold their Group C rivals to a score draw this week; teeing up an intriguing return fixture in Seville. Both teams offer a distinct threat going forward, but the tactical battle between Mourinho and Pellegrini may well end in a stalemate.