The capital club are fourth in Serie A, while their Sardinian visitors sit 13th after failing to win a league game since early November.
After a late-autumn purple patch in which everything they struck turned to goals, Roma have now won only two of their last five Serie A games, having emerged victorious from five of the previous six.
Though Paulo Fonseca's side put in a positive first-half showing versus improving Atalanta on Sunday, they then proceeded to fall apart at the seams in the second period to ultimately lose 4-1.
Star men Henrikh Mkhitaryan and Edin Dzeko combined for an early goal, with Pierluigi Gollini also making two fine saves and Leonardo Spinazzola striking the post. However, in a final half-hour display which Fonseca later described as "childish", Roma contrived to concede four goals to a Josip Ilicic-inspired side.
Though their Armenian ace Mkhitaryan - one of only two midfielders with at least six goals and six assists in the top five European leagues - racked up yet another goal-creating pass and Dzeko netted his fifth goal of the season, they again let in a flurry of goals against a direct rival, as in their 4-0 defeat to Napoli last month.
While defensive concerns are clearly an issue for Fonseca and his back three - or four, if you include below-par goalkeepers Antonio Mirante and Pau Lopez - they prepare to take on a Cagliari side which has leaked goals at a rate of nearly two per game.
Recent precedent is broadly in the Giallorossi's favour too, as in the last six meetings between the sides at Stadio Olimpico, Roma have recorded four wins and two draws.
They are also unbeaten in their last 12 Serie A matches in total against the Sardinians, with their last defeat in this encounter dating back to February 2013.
After a year which has promised much but ultimately delivered little, Roma must take advantage of their visitors' shortcomings to maintain a record of not losing their final league match of the calendar year since 2008 - with nine wins and two draws since.
Slipping down the standings after a promising start to life under Eusebio Di Francesco, Cagliari have now drawn four of their last five league games after they were held to a 1-1 home draw by Udinese at the weekend.
Di Francesco was boosted by the return of veteran centre-back Diego Godin at the Sardegna Arena following a period in self-isolation, opening up the possibility of switching to a three-man defence in future games - perhaps even to match up against Roma's standard system on Wednesday.
Though their coach lamented his charges' lack of urgency when it came to moving the ball against the Zebrette, a point was ultimately an acceptable result against a fellow mid-table team.
Formerly firing them in from all angles, Brazilian forward Joao Pedro has looked a spent force of late, while striker Giovanni Simeone has failed to register either a single goal or assist since COVID-19 infection interrupted what had been a productive start to the campaign. Just three goals from four games so far in December is testament to Gli Isolani's finishing woes.
As coach, attack-minded Di Francesco led Roma between 2017 and 2019, having previously worn the Giallorossi shirt as a player 101 times in Serie A. Returning to the scene of many treasured memories this week, the former Sassuolo boss would be relieved to return home with even a point to close out the year.
Roma Serie A form: WLDWWL
Roma form (all competitions): WDLWWL
Cagliari Serie A form: LDDLDD
Cagliari form (all competitions): WDDLDD
The Roma defence - which failed so badly in the final 30 minutes in Bergamo - should again comprise Gianluca Mancini, Chris Smalling and Roger Ibanez, with Antonio Mirante starting ahead of Pau Lopez in goal.
Centre-back Sebastian Walukiewicz should return in defence after he missed the Udinese game with a minor injury and will team up with Diego Godin from the start.
Roma possible starting lineup:
Mirante; Mancini, Smalling, Ibanez; Karsdorp, Villar, Pellegrini, Calafiori; Pedro, Mkhitaryan; Dzeko
Cagliari possible starting lineup:
Cragno; Zappa, Godin, Carboni, Lykogiannis; Marin, Rog; Nandez, Pedro, Sottil; Simeone
We say: Roma 2-0 Cagliari
Roma's year has been full of goals but they have a reputation for faltering when the going gets tough against fellow top-four contenders.
Such flakiness should not affect their final clash of 2020 though, as Cagliari's attacking limitations mean that former Giallorossi midfielder Eusebio Di Francesco will take his side back to Sardinia empty-handed for Christmas.