Both sides secured progress to the last-32 of the Europa League in midweek - in very different fashion - after enduring lamentable league results at the weekend.
Sitting fourth in the tightly-packed top section of the Serie A standings, despite an underwhelming goalless draw away to ten-man Benevento last Sunday, Roma await the arrival of former league leaders Milan in the knowledge that their home record is the best in the whole top flight. In all, the Giallorossi are unbeaten in their last 16 home league matches - winning 12 - which represents their longest such run since 2017.
Generally dominating more modest opposition but tending to crumble when facing their main top-four rivals, such as Juventus, Atalanta and city rivals Lazio - each of whom they have lost to in the past few weeks - their total domination of the ball failed to translate into all three points against Pippo Inzaghi's battling Benevento side.
Thursday's cruise through to the final 16 of the Europa League was a more straightforward affair for Paulo Fonseca's men though, as their 3-1 win over Braga sealed a 5-1 aggregate scoreline and a tie with Ukrainian champions Shakhtar Donetsk next month - the second successive round in which the Portuguese tactician has faced one of his former clubs.
However, Roma's focus must remain trained on domestic duties, as they are currently embroiled in a hotly-contested seven-way battle for European places next term. They may have closed the gap to this week's opponents to five points in recent weeks, but are also just four above seventh-placed Napoli and one clear of fierce city rivals Lazio.
After crashing out of the Coppa Italia to humble Spezia last month and having subsequently dropped off the pace in the Scudetto race, Fonseca is now expected to seal a return to the continent's top table next term and, ideally, lift the Europa League trophy to boot.
One of their chief rivals for that prestigious piece of silverware will be Milan, as their Rossoneri rivals sneaked through to the last-16 too.
Roma may have collected the most points at home this season, with 30, but Milan have posted the highest tally on the road (28). In fact, Stefano Pioli's side may be relieved to make the trip south to the capital, as some recent San Siro struggles have played a part in ending their Coppa Italia campaign and then dropping off the Serie A summit.
A draw against Red Star Belgrade at the grand old theatre of Italian football - Milan's fifth failure to win there in their last six games - proved enough to progress in Europe during the week, but only scraping past the in-form Serbian champions on away goals was not quite the tonic required after their derby day humbling against Inter in the league.
Having maintained top spot for 21 rounds, the Rossoneri had finally let first place slip due to a shock defeat against Spezia earlier this month - a result which the modest Ligurian side fully merited. Worse was to follow though, as Pioli's charges were outclassed 3-0 by their ruthless San Siro-sharing cousins in a Derby della Madonnina they will want to forget.
Though the wheels have not quite come off for a relatively young squad, Milan have now lost four Serie A games in 2021 - two more than in the entirety of last year. There is little time to mourn their losses though, as in the coming weeks - after going head-to-head with Roma - the Diavolo must also tackle Napoli and a two-legged European tie against Manchester United.
After two goalless games in Serie A, Milan could now potentially lose three top-flight matches in a row without scoring for the first time since April 1967. Undoubtedly, Pioli and his coaching staff will be working overtime to avoid that fate and get their quest for a first Scudetto in a decade back on track before relentless Inter disappear into the distance.
Roma Serie A form: LWWLWD
Roma form (all competitions): WLWWDW
AC Milan Serie A form: WLWWLL
AC Milan form (all competitions): WWLDLD
Recently reintegrated to the squad after a falling-out with coach Paulo Fonseca, former Roma captain Edin Dzeko suffered a groin strain against Braga in midweek and is likely to miss Sunday's Serie A clash. The Bosnian striker netted the opener in the first half but was forced off later on. In his absence, recent regular Borja Mayoral would be charged with leading the line up front.
In addition to the long-term injured Nicolo Zaniolo and Davide Santon, Fonseca will still be without defenders Roger Ibanez and Chris Smalling, part of the reason why he switched to a rare back four selection on Thursday. There remains the possibility of a return for Marash Kumbulla though, so the former Verona man may be fit for a spot on the bench. Previously out of favour, Federico Fazio will vie with Leonardo Spinazzola for a place on the left-hand side of Roma's three.
Milan's Ismael Bennacer and Mario Mandzukic (both with thigh problems) are expected to miss the trip to Rome, but Stefano Pioli's selection headaches of recent times - caused by a spate of injuries and illnesses - have otherwise cleared.
Soualiho Meite and Diogo Dalot will make way for Sandro Tonali and Theo Hernandez respectively, with top scorer Zlatan Ibrahimovic - out of sorts lately - coming back in to helm the attack, at the expense of Rafael Leao.
Roma possible starting lineup:
Lopez; Mancini, Cristante, Fazio; Karsdorp, Veretout, Villar, Spinazzola; Pellegrini, Mkhitaryan; Mayoral
AC Milan possible starting lineup:
Donnarumma; Calabria, Kjaer, Romagnoli, Hernandez; Kessie, Tonali; Saelemaekers, Calhanoglu, Rebic; Ibrahimovic
We say: Roma 1-1 AC Milan
Despite Milan's points advantage and status as 'winter champions', these two teams are quite equally matched, as Roma's attacking threat - particularly on home soil - is often enough to sink all-comers and the Rossoneri have descended from the crest of a months-long wave.
Nonetheless, the Giallorossi certainly suffer from a deficit in belief and composure when facing the top sides, so may be frustrated again - with a draw playing straight into the hands of both Inter and Juventus in the fight for the title.