After last minute heartbreak in Prague, Vincenzo Italiano will hope his side can pick themselves up for another shot at glory on the continent this time around.
Match preview
Losing their fourth European final left a bitter taste at the end of last season for La Viola, considering they also lost the Coppa Italia final to Inter Milan.
Fiorentina have not made an ideal start to this campaign either, showing inconsistency with some big wins and chastening defeats.
Scoring nine goals in their first four Serie A games suggests that they have made a strong start, and a thrashing of Genoa and an impressive win over Atalanta suggests they have.
However, losing 4-0 at Inter and drawing with Lecce were big low points so early in the campaign.
Italiano's men limped through qualifying too after being a late entry to the competition following Juventus' expulsion over the summer.
Rapid Vienna very nearly ended their European season before it even began though, winning the first leg in Austria.
It took an injury-time penalty from star man Nicolas Gonzalez to complete the turnaround in Florence, as last year's runners-up now take their place in a group that contains Ferencvaros and Cukaricki.
The draw will mean that these two sides should fancy their chances of progression.
After winning just one of their first five games this season, Genk have returned to form just in time for their group stage opener.
Their poor start saw them slip from the Champions League to the Europa League and then the Europa Conference League.
However, just one defeat in their last seven has seen them reach the group stage and start strongly in the Belgian Pro League.
Genk's only loss in that time came in their second leg playoff against Adana Demirspor, which they would eventually go on to win on penalties anyway.
Two tough league games since have yielded four well-earned points for Wouter Vrancken's side, with a 1-1 draw against Anderlecht after playing with 10 men for over three-quarters of the match and a 2-0 victory at Union Saint-Gilloise.
Home form has been slightly underwhelming though, as the first leg win over Adana Demirspor remains their only success here this season.
Picking up points at home will be crucial if Genk are to progress past the groups in Europe for the first time since 2018.
The Belgian's best-ever run in Europe saw them reach the quarter-finals in 2016-17 before going down to Celta Vigo, but their first ever experience of the Conference League provides a better opportunity for the club to go far.
Genk Europa Conference League form:
W
W
Genk form (all competitions):
D
D
W
W
D
W
Fiorentina Europa Conference League form:
L
W
Fiorentina form (all competitions):
W
L
D
W
L
W
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Team News
Genk will be able to welcome back Christopher Bonsu Baah after his domestic suspension following a red card against Anderlecht.
Andi Zeqiri scored on debut in their win at Union SG at the weekend, but there has been no notable arrival who looks set to replace Mike Tresor out wide, after he got 25 assists last season.
Tolu Arokodare has been in good form, scoring twice off the bench so far this season, and he will compete with Joseph Paintsil for a starting spot.
Fiorentina will be able to call upon new signing Maxime Lopez for the first time after his arrival from Sassuolo.
A red card in his final game for the Neroverdi has meant Sofyan Amrabat's replacement has not kicked a ball in a purple shirt yet, but he should feature here.
Yerry Mina will be unavailable after his persistent muscular problems arose again while on Colombia duty.
There are also heavy doubts regarding the fitness of Jonathan Ikone and Gaetano Castrovili, but Antonin Barak returned from injury at the weekend to make a late cameo off the bench.
Cristiano Biraghi did not start, but the Fiorentina captain should take the place of Fabiano Parisi at left-back.
M'Bala Nzola will hope for another chance from the start up front to try to break his duck since arriving from Spezia to replace Benfica-bound Arthur Cabral.
Genk possible starting lineup:
Vandevoordt; Munoz, Cuesta, Sadick, Kayembe; Heynen, Galarza, Hrosovsky, El Khannous; Zeqiri, Paintsil
Fiorentina possible starting lineup:
Terracciano; Dodo, Milenkovic, Martinez Quarta, Biraghi; Mandragora, Lopez, Bonaventura; Gonzalez, Kouame, Barak
We say: Genk 1-2 Fiorentina
Fiorentina have been up and down in the early stages of the season, but a win over Atalanta at the weekend should bring great confidence to the side for their trip to Belgium.