Curiously, both sides have played Crotone and Sampdoria since the winter break - with Roma taking maximum points and Inter collecting just three after a shock defeat in Genoa.
Inter and Roma have drawn all of their last five Serie A encounters with each other - a sign of how well-matched the two clubs have been in recent seasons - but both will be eager to claim a win this time as they pursue league leaders AC Milan.
Antonio Conte's side were unfortunate to lose against Sampdoria in midweek, as Alexis Sanchez - standing in for Romelu Lukaku - saw an early penalty saved before Nerazzurri old boys Antonio Candreva and Keita Balde netted for Samp.
Stefan de Vrij's second-half header failed to provoke a comeback, with Inter ending a run of eight straight wins in frustrating fashion.
That 'consolation' goal came within minutes of Lukaku's arrival from the bench - despite the Belgian forward carrying a thigh problem - and defeat after just seven of their 24 shots hit the target only served to demonstrate Inter's reliance on their star striker.
Though he moved onto nine goals for the campaign with a recent hat-trick, Lautaro Martinez has often been wasteful and sometimes struggles when paired with Sanchez.
All is far from lost for the Nerazzurri, however, as table-topping city rivals Milan also lost to leave them just one point behind in an increasingly close Scudetto contest.
Only Juventus can match Inter's squad depth as the season continues through a packed midwinter schedule, with players such as Achraf Hakimi - two goals and one assist in the last four games - and midfield regulator Marcelo Brozovic (three assists from three) now starting to shine.
They have lost two league games in a row only once under Conte's leadership, versus Lazio and Juventus early last year. The former Chelsea coach will do all within his power to prevent that happening again in Rome.
Paulo Fonseca's Roma side emulated Inter's recent routine victory over struggling Crotone - whose defence is statistically one of the worst in Europe - on Wednesday.
Their flying visit to sunny Calabria saw them depart Stadio Ezio Scida with all three points to stay just ahead of Juventus, Atalanta and Napoli in the standings.
Fonseca later commented that Roma were unlikely to change their well-defined system in order to let the pair play together against Inter, but did not rule the possibility out in the future.
Certainly, the capital club have not been short of goals in any case, as Roma scored three or more first-half goals for a third Serie A match this term against Crotone.
Not only that, but in contrast to striking some bumps while on the road, the Giallorossi are unbeaten in their last 12 league home games - winning nine - which is their longest such streak since 2017, when they went 24 without defeat.
With the Derby della Capitale to follow next Friday, this could prove a pivotal week for Fonseca's charges as they seek to establish themselves as genuine dark horses in the title race.
Roma Serie A form: WWDWWW
Inter Milan Serie A form: WWWWWL
Inter defender Danilo D'Ambrosio injured the medial collateral ligament in his left knee last time out and could be missing for a substantial period, while Matias Vecino and young striker Andrea Pinamonti are both still out through injury for Conte's team.
Lukaku is set to return to the attack after Sanchez failed to impress against Sampdoria, so the former Manchester United man will partner Martinez up front in Conte's familiar 3-5-2.
Dzeko and spot-kick specialist Jordan Veretout, who have both netted seven goals to date, return to the Roma first XI on Sunday, with Mayoral and either Bryan Cristante or Gonzalo Villar dropping out.
In addition to Pedro - whose absence should be covered by Lorenzo Pellegrini - defender Federico Fazio, goalkeeper Antonio Mirante plus longer-term absentees Javier Pastore and Nicolo Zaniolo are still unavailable, though wing-back Davide Santon has returned to training and could make the bench.
Roma possible starting lineup:
Lopez; Mancini, Smalling, Ibanez; Karsdorp, Villar, Veretout, Spinazzola; Pellegrini, Mkhitaryan; Dzeko
Inter Milan possible starting lineup:
Handanovic; Skriniar, De Vrij, Bastoni; Hakimi, Barella, Vidal, Brozovic, Young; Lukaku, Martinez
We say: Roma 2-2 Inter Milan
This box-office lunchtime showdown has all the makings of a classic encounter, with much already at stake before Serie A has even reached its halfway point.
Roma's scintillating attacking patterns could unsettle an Inter defence that has improved but conceded twice in both of their last two games - but Lukaku's return to the starting lineup can inspire the dogged visitors to fight fire with fire at the Olimpico.