The teams convene in the Czech capital, with the Viola's last silverware coming some 22 years ago and the Hammers having waited almost twice as long. One will now succeed inaugural winners Roma, as the competition's top scorers clash with unbeaten opponents.
Match preview
Three decades after their most recent European final appearance - a defeat to Serie A rivals Juventus in the 1990 UEFA Cup showpiece - Fiorentina will become the first club to feature in all four UEFA club competition finals when they stride out on Wednesday night.
Vincenzo Italiano's men will also follow in the footsteps of Viola sides that have featured in the European Cup and Cup-Winners' Cup deciders, having forged their own path to Prague in impressive style this season.
Comfortably the Europa Conference League's leading scorers, Fiorentina have racked up some 36 goals in 14 games during the process - nine more than second-ranked West Ham, albeit having played two more matches.
With Brazilian striker Arthur Cabral setting the pace on seven strikes so far, 21 of those goals were scored away from home, and the Viola have netted at least three times on each of their last six European road trips; winning on each occasion.
The Tuscan club have actually lost three matches already: finishing runners-up in Group A, before brushing aside Braga, Sivasspor and Lech Poznan to make the semi-finals, where Basel lay in wait. It took extra time to see off the stubborn Swiss side, and Antonin Barak's late winner helped avoid the lottery of penalties; setting up the chance to become Italy's second successive Conference League winners.
By rallying towards the end of their domestic season, Fiorentina finished eighth in Serie A when the campaign concluded last weekend, and a run of three wins from four ended with Friday's 3-1 win at Sassuolo.
Nonetheless, only if Juventus are ultimately banned from UEFA competition will the Viola qualify for more European football next term, so with Wednesday's winners gaining direct entry to the 2023-24 Europa League group stage, the stakes are even higher when they meet West Ham.
While Italiano has been lauded for introducing a slick style of play and reviving Fiorentina's flagging fortunes, the pressure is now on to secure silverware for a club whose last major trophy was the Coppa Italia of 2001. Failure in this year's cup final versus Inter saw one shot at glory come to nothing, so everything now rides on the season finale.
Fiorentina have not won a continental title since the 1961 European Cup-Winners' Cup, while West Ham won the same trophy four years later, when they beat 1860 Munich 2-0 at Wembley. Neither side has lifted a UEFA trophy since, but it is the Hammers who have had to wait longest for silverware of any sort.
Few would have thought FA Cup victory in 1980 would be followed by a 43-year drought, but that is what transpired at the East London club, who in addition to several domestic near-misses fell in the Europa League semi-finals last season.
David Moyes has since managed to navigate some stormy seas while several colleagues at other Premier League clubs were fired for underperformance, and the experienced Scot has now taken West Ham one step further in the Conference League.
Despite not always fielding his strongest side on Thursday evenings, Moyes has seen his team put together an impressive unbeaten record throughout Europe's third-tier competition - with only one draw blotting an otherwise perfect return from 12 matches.
Their route to the final took in winning Group B last autumn, before beating both AEK Larnaca and Gent quite comfortably in the knockout stages; a 3-1 aggregate defeat of AZ Alkmaar in the semis featured some ugly scenes in the away leg, but despite crowd trouble threatening to mar the moment, a final place was secured.
The Hammers' continental campaign, though, has developed in contrast to dismal domestic form for most of the 2022-23 season, and they had to settle for a 14th-place finish after losing 2-1 to Championship-bound Leicester City on the Premier League's final day.
Some have suggested that the future of Moyes and his coaching staff could still depend on the outcome in Prague, as over £150m was spent last summer to little effect. Surely shifting the burden of going generations without a trophy would make him untouchable though.
Fiorentina Europa Conference League form:
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West Ham United Europa Conference League form:
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West Ham United form (all competitions):
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Team News
Once again, Vincenzo Italiano rotated his Fiorentina squad at the weekend, in order to keep key men fresh for Wednesday's showpiece occasion, and with most players available he will be tasked with settling on his strongest XI.
Only back-up goalkeeper Salvatore Sirigu is sidelined by injury, while Nicolas Gonzalez should be fit to start despite crashing into the goalpost in scoring the Viola's final goal of the Serie A season.
Having also netted twice in last month's win over Basel, the Argentina winger should support central striker Arthur Cabral from the right, but other places in Italiano's attacking unit appear up for grabs.
Czech playmaker Antonin Barak is among those in contention: the semi-final matchwinner played for final hosts Slavia Prague prior to moving to Italy.
Both Tomas Soucek and Vladimir Coufal also turned out at the Fortuna Arena during their time at the same club, and the pair should feature for West Ham in midweek.
Joining Soucek in the English side's engine room, captain Declan Rice will most likely sign off on his Hammers career before departing for pastures new this summer. Elsewhere, cup goalkeeper Alphonse Areola replaces Premier League first-choice Lukas Fabianski.
Gianluca Scamacca - recently linked with a loan move back to Serie A in the summer - is set to be West Ham's sole absentee, having recently undergone knee surgery. With his place almost uncontested, then, Michail Antonio starts up front.
Fiorentina possible starting lineup:
Terracciano; Dodo, Martinez Quarta, Milenkovic, Biraghi; Amrabat, Mandragora; Gonzalez, Bonaventura, Ikone; Cabral
West Ham United possible starting lineup:
Areola; Kehrer, Aguerd, Zouma, Cresswell; Soucek, Rice; Bowen, Paqueta, Benrahma; Antonio
We say: Fiorentina 1-2 West Ham United
As Fiorentina are not likely to compromise on their principles and could take the game to West Ham, an intriguing encounter is in prospect. Both teams are desperate to claim silverware, though, and it may be a tempestuous affair.