The new German champions seek revenge for losing in last season's semis and aim to meet either Marseille or Atalanta BC in this term's Dublin decider; meanwhile, the hosts boast an abundance of know-how from their recent exploits in Europe.
Match preview
Emerging triumphant from an all-Italian tie in the Europa League quarter-finals, Roma finished the job against AC Milan after earning a slim lead from the first leg at San Siro and then winning 2-1 on home turf one week later.
Gianluca Mancini struck for a second time in the tie, before Paulo Dybala produced the killer blow soon after, and despite Zeki Celik's subsequent dismissal, the Giallorossi held on; extending their quest to make a third straight European final - but the first without former boss Jose Mourinho.
Mourinho's men eked out a 1-0 aggregate win over Leverkusen in last year's semis before losing to competition specialists Sevilla in the final, only 12 months after lifting the inaugural Europa Conference League trophy.
There have still been no Serie A successes since the Europa League replaced the UEFA Cup in 2009, but Roma and Atalanta BC have been kept apart in the semi-final draw and could yet meet in this season's decider.
Should they get that far, the Giallorossi will be led out by club legend and current coach Daniele De Rossi, who has overseen 13 wins and just three losses in 20 games since taking temporary charge in January, following Mourinho's sacking.
De Rossi recently extended his contract in the capital and is now trying to sign off for the season by claiming some silverware and securing a top-five place in Serie A, thereby securing Champions League football for next term.
His side still occupy fifth place in the standings, just ahead of Atalanta, but following a 2-2 draw in last week's Derby del Sole, they still have plenty of work remaining.
Indeed, it took a late Tammy Abraham equaliser to salvage that point against Napoli, while Roma lost a recent clash with fourth-placed Bologna; yet they could still claim a place at Europe's top table by winning the Europa League.
Though Leverkusen also drew 2-2 last time out, their domestic situation contrasts somewhat with Thursday's hosts, as they were sensationally crowned German champions with several weeks to spare.
The Bundesliga winners struck a last-gasp equaliser for the third time running to deny Stuttgart at the weekend, taking their remarkable unbeaten streak to 46 games in all competitions, of which they have won some 38.
The 44th match in that sequence was the 1-1 draw at West Ham United that booked a place in the Europa League semi-finals, and Jeremie Frimpong's late leveller helped set a new all-time mark for games undefeated throughout Europe's top five leagues.
Naturally, Die Werkself's top-flight points and goals tallies - 81 and 77, respectively - are both club records to this point of a season, and the admirable leadership of Xabi Alonso has seen the club finally shake off their 'Neverkusen' tag.
Also awaiting a trip to Berlin for the DFB-Pokal final, in which they will start favourites against rank outsiders Kaiserslautern, an historic treble is on the cards - the minor matter of becoming the first team to go through an entire Bundesliga campaign without losing is still up for grabs too.
Like De Rossi, the much-sought Xabi Alonso has confirmed he will stay put at his current club for another year at least, and a fascinating duel between two up-and-coming coaches will unfold over the next week, with the first act taking place in Italy's 'Eternal City'.
Roma Europa League form:
D
W
W
L
W
W
Roma form (all competitions):
W
W
W
L
W
D
Bayer Leverkusen Europa League form:
W
W
D
W
W
D
Bayer Leverkusen form (all competitions):
W
W
W
D
D
D
Team News
While Roma will be without right-back Zeki Celik - who is suspended after being sent off in the second leg against Milan - Bryan Cristante is back from a European ban; Diego Llorente and Leandro Paredes are both available after serving suspensions in Serie A last weekend.
Europa League specialist Romelu Lukaku - who has scored seven goals in this season's competition and 27 times overall - has resumed full training after missing the trip to Naples, so he should spearhead the hosts' attacking trident, with Sardar Azmoun and Tammy Abraham consigned to the bench.
Captain Lorenzo Pellegrini has enjoyed more freedom under Daniele De Rossi and is set to overcome a minor muscular problem to feature in midfield.
Chris Smalling could return from his latest injury in time to play some part too, but fellow defenders Rasmus Kristensen and Dean Huijsen were not included in the Giallorossi's UEFA squad list for the knockout stages.
Lukaku's ability to score in the Europa League may be almost unparalleled, but no player has created more chances from open play (24) in this term's tournament than Leverkusen's Florian Wirtz, who has also netted 11 career goals in the competition at the tender age of 20.
Die Werkself's midfield fulcrum Granit Xhaka returns from suspension, after being sidelined for the draw against Stuttgart, so either Robert Andrich - who scored their 96th-minute goal on Saturday - or Exequiel Palacios must miss out.
Only Adam Hlozek and Borja Iglesias are injury doubts for the visitors, but both could yet be involved on Thursday evening.
Roma possible starting lineup:
Svilar; Karsdorp, Mancini, Ndicka, Angelino; Cristante, Paredes, Pellegrini; Dybala, Lukaku, El Shaarawy
Bayer Leverkusen possible starting lineup:
Hradecky; Kossounou, Tah, Hincapie; Frimpong, Palacios, Xhaka, Grimaldo; Wirtz, Adli; Schick
We say: Roma 1-1 Bayer Leverkusen
The impetus is on Roma to take a first-leg lead, due to their weak away record, so the hosts cannot simply sit back and soak up pressure at a packed Stadio Olimpico. Leverkusen have shown they are not impregnable in recent weeks, but having scored some 17 goals after the 88th minute this season, another late strike may send them back to Germany on level terms.