After opening their group stage campaign with a draw, the Giallorossi are the guests for the first ever Champions League game on Azerbaijan soil.
Roma are heavily favoured to grab the victory, but almost 70,000 fans are expected at a sold-out Baku National Stadium to cheer on their heroes. Can Eusebio Di Francesco's side ignore the atmosphere and successfully spoil the party?
The pre-match reading
The form guide
Qarabag made their Champions League bow with a heavy 6-0 defeat against Premier League champions Chelsea, and will be looking to respond strongly back on home soil.
The reigning champions are unbeaten in the domestic league this season, winning their last two matches by 2-0 and 4-1 margins. They sit top of the table with five wins from five, thanks in part to five goals from forward Mahir Madatov.
Since opening their Champions League campaign with a slightly nervy 0-0 draw with Atletico Madrid, the Giallorossi have won their last three games on the spin, scoring 10 goals in the process (and conceding just one, in the final moments of Sunday's 3-1 win over Udinese).
Edin Dzeko and Stephan El Shaarawy have both been among the goals, while the group has started to look settled and compact at the back too.
Roma are still without forward Patrik Schick and full-backs Nura Abdullahi and Rick Karsdorp, who are working their way back to full fitness after recent issues.
Centre-back Hector Moreno skipped the trip to Baku after suffering a slight knock in training on Monday, although he is expected to be available again before Sunday's visit to AC Milan.
Diego Perotti travelled with the group despite suffering a deep cut to his ankle during the win over Udinese. However, he did not complete Tuesday's pre-match training session and as a result may be a doubt for the contest.
Elsewhere, both Emerson Palmieri and Leandro Castan are not registered for this phase of the competition.
Qarabag's main doubt is over defender Ansi Agolli, who has been injured but did train with the group on Tuesday.
Elsewhere, Anton Kanibolotskiy could usurp Ibrahim Sehic in goal, after the latter played against Chelsea - while Elvin Yunuszada could replace Rashad Sadygov after a solid performance at the weekend.
The view from the dugout
Gurban Gurbanov: "It will be our first home match in the group stage of the Champions League. I think it's very important for all of us. This game will be very significant for our country and our football.
"Maybe some people see Roma as not that strong a team in our group, but I've watched them and can say they're a very professional outfit. Nevertheless, we'll try to get a positive result tomorrow."
Eusebio Di Francesco: "With all the games we're playing at the moment we need to get everyone involved but the squad we've got here has been put together so that I have players ready to do the business in every single match.
"And tomorrow is an important match. We must show Qarabag the respect they and their history deserve. I can assure you it will be no easy game.”
Opposition danger man
In truth, the young forward will surely be delighted if he gets more than a couple of half-chances in front of the Roma goal on Wednesday night. But it is clear that the 20-year-old is an intriguing prospect for Qarabag - and their most dangerous attacking threat.
The youngster already has 15 goals for his club (and five already this season), an impressive return for someone barely out of their teens. Dangerous from distance and on either foot, European competition might be a big leap in standard for him - but how he fares will be an interesting gauge of his longer-term potential.
“He's a very talented player," Di Francesco said at his pre-match press conference. "He's skillful and he's scored lots of superb goals from long range.
"The main reason I've come here is to win but of course Qarabag have some fine players who are capable of hurting opponents.”
Roma's one to watch
STEPHAN EL SHAARAWY
Over the injury problems that derailed the start of his campaign, El Shaarawy grabbed his first and second goals of the season on Sunday - and will likely go straight back into the starting line-up for this one.
Praised as one of the "ideal" forwards for the attacking system he wants by coach Di Francesco, El Shaarawy will be riding high at the moment, and his combination of pace, skill and eye for goal should prove a prospect that Qarabag struggle to deal with over the course of the 90 minutes.
Coach Eusebio Di Francesco has consistently promised rotation and rest for his players throughout what is a heavy run of fixtures, with a visit to AC Milan looming on Sunday.
The coach indicated there could be five changes from Sunday's line-up ... although he may make many fewer. Lorenzo Pellegrini, Juan Jesus, Bruno Peres and Cengiz Under would seem the likeliest players to come into the side on this occasion.
Coach Gurbin Gorbanov has promised a couple of changes from the side that lost against Chelsea.
"We will make some changes from the match against Chelsea because these two opposition teams are very different," he noted. "But you will not see many.
"Defender Ansi Agolli is injured and we will decide if he plays after training tomorrow morning. There's a possibility that he'll play."