While the Serie A side lost 2-1 in Bulgaria on the opening day and are level on points with their visitors before this week's return, they can leapfrog them into second place with a win; Ludogorets must simply avoid defeat.
Match preview
Accustomed to high-stakes continental encounters, having gone all the way to the final and won last season's inaugural Europa Conference League, Jose Mourinho's Roma will face another must-win moment when the Bulgarian champions arrive in Italy's capital.
The prize for victory would be entry to the Europa League's knockout round playoffs as runners-up behind Real Betis; otherwise they will take the back route to an unwanted Conference League return.
Somewhat fortunate to prevail on a plastic pitch in Helsinki last week, the Giallorossi's 2-1 win over rock-bottom HJK at least keeps them in control of their own destiny, having previously taken only a point from back-to-back games with Betis.
After Tammy Abraham's header and an Arttu Hoskonen own goal earned three precious points in Group C, Roma returned to domestic action on Monday night, and a dramatic late comeback saw them snatch victory against Verona - young Cristian Volpato scoring in the 88th minute, before Stephan El Shaarawy secured a 3-1 win in stoppage time.
They may still be seven points adrift of irrepressible leaders Napoli, but Mourinho's men sit fourth in the Serie A standings - one point above city rivals Lazio, who are also taking part in a Europa League decider on Thursday.
The pair meet in a much-anticipated Derby della Capitale this weekend, but before that battle for capital city supremacy kicks off, Roma aim to commence another long unbeaten run at home in Europe, like the 20-match one ended by Betis last month. However, they have lost three of their last four games at the Olimpico in all competitions.
Following his side's 1-0 defeat to undisputed group winners Real Betis last week, Ludogorets coach Ante Simundza claimed the better side had lost; nevertheless, taking no points from two fixtures with the Seville club has left their qualification for the next phase in a perilous position.
Ahead of Roma on the clubs' head-to-head record after a famous victory in Razgrad on the opening day, the Bulgarian champions will enter the knockout round playoffs as runners-up if they avoid defeat on Thursday; meeting a Champions League drop-out for the right to a place in the last 16.
Otherwise, they are bound for the Conference League, so there can be no doubt about the nature of the task facing Simundza's men in their final group game.
Ludogorets are currently winless in 11 away matches in the Europa League, though, and such a dismal run has featured a total of eight losses. They have also failed to keep a single clean sheet during that time.
Although they currently sit five points behind Bulgarian First League leaders CSKA Sofia, the Eagles have two games in hand on their closest rivals and have won each of their last four domestic matches - including a crucial 2-1 success over CSKA.
Defending their title, then, seems well within reach. More immediately, though, the lure of European glory will be spurring them on to secure a spot in next week's Europa League draw, after which another glamour tie could await in the playoffs.
Roma Europa League form:
L
W
L
D
W
Roma form (all competitions):
W
D
W
L
W
W
Ludogorets Razgrad Europa League form:
D
W
L
D
W
L
Ludogorets Razgrad Europa League form:
Team News
Roma are set to make several changes to their lineup in midweek, as Sunday's Rome Derby takes precedence, yet Jose Mourinho will also be keen to progress in Europe.
Still without Paulo Dybala due to injury, the Giallorossi also have Georginio Wijnaldum and Leonardo Spinazzola sidelined, with the latter's absence opening the door for Nicola Zalewski to feature on the left flank.
Cristian Volpato could be rewarded for his recent impact on the first team by earning another start in support of the hosts' main striker, which may be Andrea Belotti if Tammy Abraham is rested ahead of the weekend. Meanwhile, Mady Camara and Nemanja Matic battle it out for a place in midfield.
Ludogorets boss Ante Simundza is expected to name a similar side to that which lost against Betis last time out, with Thiago leading the line up front, though Kiril Despodov and Matias Tissera are both pushing for a start too.
Another Brazilian, Cauly, scored the opening goal when these side last met, back in early September, and should take up an advanced midfield role on Thursday.
Roma possible starting lineup:
Patricio; Ibanez, Smalling, Mancini; Celik, Cristante, Camara, Zalewski; Pellegrini, Zaniolo; Belotti
Ludogorets Razgrad possible starting lineup:
Padt; Fonn Witry, Verdon, Nedyalkov, Gropper; Piotrowski, Naressi; Tekpetey, Cauly, Rick; Tissera
We say: Roma 2-1 Ludogorets Razgrad
While Ludogorets pose a significant threat back in Bulgaria - as evidenced in Roma's defeat there earlier this term - they do not tend to travel well; making them susceptible to a last-day defeat.