Soon to aim for Champions League glory, Inter won their eighth national cup last year and have claimed the Supercoppa Italia already this term; meanwhile, the Viola are also preparing for a European final and want to end a 22-year trophy drought.
Match preview
In addition to dumping their city rivals out in the semis of Europe's top club competition, Inter took great delight in eliminating old foes Juventus from the Coppa Italia when the two Calcio giants met last month.
Having also beaten Juve in the final 12 months ago and seen off Milan to lift the Supercoppa in January, there is no doubt that the Nerazzurri are cup specialists under the management of Simone Inzaghi; Parma and Atalanta were also swept aside on this year's route to Rome.
While they recently suffered their 12th defeat of an inconsistent Serie A season - Sunday's 3-1 defeat to new champions Napoli - Inter are still closing in on a top-four finish, thanks to a previous winning streak of eight games in all competitions.
That represents quite a turnaround for Inzaghi, who before that run was fending off questions about his future at San Siro: when his team were beaten 1-0 by Fiorentina at the start of April, it was the first time in six years Inter had lost three on the spin in Serie A.
There is still plenty of pressure on his shoulders to claim silverware after such a lacklustre league campaign, but victory in Rome and then Istanbul - where the Nerazzurri clash with Manchester City next month - would see his name join 2010 treble-winner Jose Mourinho's in club folklore.
One of three Serie A sides soon to contest European finals, Inter meet another in Wednesday's Coppa Italia showpiece, and they will hope the outcome resembles their success in a 4-3 thriller last October - when Henrikh Mkhitaryan found a last-gasp winner in Florence - rather than their tame defeat on home turf.
Such was their prior dominance in this match-up, Inter had gone unbeaten in 11 league games versus the Viola before ex-Milan man Giacomo Bonaventura scored the second-half decider when the teams most recently met at San Siro.
Fiorentina have toiled in the shadow of their counterparts from the second city, then, but more recently the Tuscan club have begun to close the gap just a little - thanks to the impact of coach Vincenzo Italiano.
The former Spezia boss was only brought in when Gennaro Gattuso's appointment went awry, but since his arrival in the summer of 2021, Fiorentina have played some spectacular football - if only intermittently - and are now two games away from double cup glory.
Like Inter, last week they progressed from a continental semi-final; in their case seeing off Basel in extra time to set up a Europa Conference League contest with West Ham United in Prague next month.
Having already conquered Cremonese, Torino and Sampdoria to reach the Coppa Italia's last two, Italiano's men can go down in history should events unfold in their favour over the next fortnight - though their Serie A season has been something of a disappointment.
Bedevilled by inconsistency for most of the campaign, Fiorentina sprang into life and won nine of 10 matches leading into their semi-final tie with giantkillers Cremonese - who had already knocked out both Roma and Napoli - but following a 1-1 draw with Torino last time out they are yet to confirm even a top-half finish.
Therefore, it's a case of all-or-nothing in the cups, as they seek to end their search for a first trophy since Roberto Mancini's side beat Parma to the Coppa back in 2001.
Fiorentina Coppa Italia form:
W
W
W
D
Fiorentina form (all competitions):
D
L
L
W
W
D
Inter Milan Coppa Italia form:
W
W
D
W
Inter Milan form (all competitions):
W
W
W
W
W
L
Team News
After a much-changed team started when Inter's winning run came to its end in Naples, Simone Inzaghi is set to select a side similar to that which saw off Milan last week.
Therefore, Joaquin Correa and Romelu Lukaku should be replaced by Lautaro Martinez and Edin Dzeko up front, while several other first-choice picks return to the lineup.
Only long-term absentee Milan Skriniar (back) and Henrikh Mkhitaryan (thigh) will miss out due to injury, and the latter's absence in midfield should be covered by Marcelo Brozovic.
Club captain Samir Handanovic is expected to start in goal - ahead of Andre Onana, who will instead play in the Champions League final. Handanovic started in the semi-final first leg against Juventus but was then suspended for the return due to receiving a red card after the final whistle in Turin.
Fiorentina, meanwhile, are a more unpredictable proposition, as while Inzaghi rarely strays from his favoured personnel in a classic 3-5-2, Vincenzo Italiano tends to tinker more.
Several key players were rested in Sunday's draw with Torino, so Sofyan Amrabat, captain Cristiano Biraghi and top scorer Arthur Cabral will be among those brought back into the Viola's starting XI in midweek.
Giacomo Bonaventura returns from a Serie A suspension and is set to feature in midfield, but Salvatore Sirigu has seen his season ended by an Achilles injury and will watch on from the sidelines.
Fiorentina possible starting lineup:
Terracciano; Dodo, Milenkovic, Igor, Biraghi; Bonaventura, Amrabat, Mandragora; Gonzalez, Jovic, Ikone
Inter Milan possible starting lineup:
Handanovic; Darmian, Acerbi, Bastoni; Dumfries, Barella, Brozovic, Calhanoglu, Dimarco; Martinez, Dzeko
We say: Fiorentina 1-2 Inter Milan
Even accounting for their second-string's weekend defeat, Inter have won seven of their last eight matches - and by an aggregate score of 23-6.