Two points separate the sides at the halfway stage of the group, with Roma knowing that victory over the Premier League champions would leave them in pole position to qualify for the last 16 as group winners.
Unbeaten in this season's group stages so far, Roma head into Tuesday night's match looking to take a big step towards the knockout stages of the Champions League for only the second time since 2011.
The draws have not been kind for the Serie A outfit in recent years, facing Bayern Munich and Manchester City in the 2014-15 groups, Barcelona in the 2015-16 groups before being eliminated by Real Madrid in the knockout rounds and then coming up against Chelsea and Atletico Madrid in this season's competition.
So far, though, Roma have held their own against their fellow last-16 hopefuls, playing out a goalless draw with Atletico on matchday one before their infinitely more entertaining 3-3 draw with Chelsea at Stamford Bridge a fortnight ago.
Roma came from two goals down to lead 3-2 in that match before Eden Hazard rescued a point for the home side, but having come away from West London with a draw they will be confident of going one better in Rome.
Roma have only lost one of their last eight matches at the Stadio Olimpico across all competitions, including four wins from six matches this season during which they have conceded only two goals.
It is a different story in the Champions League, though, with Roma not having scored a home goal in this competition since November 2015, drawing four blanks in a row since a 3-2 victory over Bayer Leverkusen.
Indeed, that win over Leverkusen is their only Champions League triumph at the Stadio Olimpico from their last eight attempts including qualifying, while home and away the capital outfit have won just two of their last 18 Champions League games.
Roma's next two matches are likely to be pivotal for their chances of reaching the knockout rounds as they take on Chelsea and Atletico, although the Madrid club's poor form - which has seen them pick up only two points from an available nine so far - does give Eusebio Di Francesco's side some breathing space.
Last season's Serie A runners-up are also amongst the leading pack on the domestic front too, although they currently sit fifth in what is shaping up to be the most competitive Italian title race in recent years.
Recent Champions League form: DWD
Recent form (all competitions): WLDWWW
Tuesday night could prove to be a pivotal one for Chelsea's Champions League campaign; defeat would see them slip down into second place, but victory would be enough to seal a spot in the last 16 with two games still to spare.
The Blues currently sit two points clear of Roma having dropped their first points of the group stages in the reverse fixture a fortnight ago, and crucially they are now five points clear of Atletico - meaning that they would guarantee their place in the knockout stages with a win in Rome.
Antonio Conte will not need telling how difficult that task will be, though, having previously managed Atalanta and Juventus in Serie A and also seeing Roma's impressive performance en route to their point at Stamford Bridge.
The draw with Roma made it three matches without a win for Chelsea, but they have since won all three of their subsequent outings, albeit without looking entirely convincing in any of them.
A 1-0 win over struggling Bournemouth at the weekend was deserved, but they will need to be more ruthless in front of goal if they are to come away with all three points from the Stadio Olimpico too.
A huge showdown with high-flying Manchester United awaits on Sunday with Chelsea knowing that defeat could leave them 12 points adrift of leaders Manchester City, so this is a big week for the club both domestically and in Europe.
Victories over Qarabag and Atletico have left them in a strong position on the latter front, and another win on Tuesday would put them on the verge of finishing top of their Champions League group having missed out on the competition for the first time since 2003-04 last season.
Chelsea have only lost two of their last nine European away games too, although a win in Rome would hand them back-to-back Champions League triumphs on the road for the first time since 2013.
To achieve that in Madrid and Rome would be some feat for Conte's side, and with five wins from their six away outings across all competitions this season there will be plenty of people backing Chelsea to do just that.
Recent Champions League form: WWD
Recent form (all competitions): LLDWWW
Conte has hinted that N'Golo Kante could feature on Tuesday having missed the last four games with a hamstring injury, although the Ballon d'Or nominee is unlikely to be thrown straight back into the starting XI.
Victor Moses is the only other injury concern for Chelsea heading into the game, although Conte does have a number of decisions to make in terms of personnel and may keep Sunday's match against Manchester United in mind too.
David Luiz featured in a midfield role in the reverse fixture and opened the scoring from that position, but the Brazilian is expected to revert to a more defensive position on Tuesday.
Roma are expected to be without Kostas Manolas once again due to a thigh strain, while summer signing Rick Karsdorp faces a lengthy spell on the sidelines after rupturing his ACL on his debut against Crotone last Wednesday.
Roma possible starting lineup:
Alisson; Florenzi, Fazio, Jesus, Peres; Pellegrini, De Rossi, Strootman; Defrel, Dzeko, El Shaarawy
Chelsea possible starting lineup:
Courtois; Rudiger, Luiz, Cahill; Azpilicueta, Fabregas, Bakayoko, Alonso; Pedro, Morata, Hazard
Head To Head
The reverse fixture a fortnight ago ended 3-3 at Stamford Bridge, with Edin Dzeko scoring twice to help Roma recover from two goals down before Hazard ensured that the spoils were shared.
These two clubs had only met on two previous occasions before that, both of which came in the 2008-09 Champions League group stages and both of which went the way of the home side.
John Terry scored home and away that season as Chelsea ran out 1-0 winners at Stamford Bridge before falling to a 3-1 defeat in the reverse.
Roma have won eight and lost four of their 15 previous home games against English clubs, although that does not include their 1984 European Cup final defeat at the hands of Liverpool, which occurred at the Stadio Olimpico.
Chelsea, meanwhile, have only ever won one of nine previous visits to Italy, including defeats on each of the past three trips.
We say: Roma 2-1 Chelsea
This match is unlikely to be as open and goal-laden as the reverse at Stamford Bridge, with Roma having had some low-scoring results at home recently. Chelsea are not at their best right now, despite three consecutive wins, and a trip to the Stadio Olimpico may prove a step too far for them at the moment.