Udinese must overcome a shock first-leg loss to Slovan Liberec if they wish to progress to the UEFA Europa League group stage on Thursday.
The Italians were stunned 3-1 at their home ground by the Czech Republic side, who are in excellent form having won 12 of their last 15 competitive matches.
Veteran striker Antonio Di Natale scored in both legs of Udinese's third-round qualifying match against Siroki Brijeg and the Serie A club will need the Italian international firing on all cylinders again if it is to overturn the deficit against Liberec.
Fellow Italian side Fiorentina will take a slender 2-1 advantage into their second leg at home against Switzerland's Grasshopper.
With two away goals in Zurich, Fiorentina will be favourites to progress but the plucky Swiss side could surprise.
English Premier League side Tottenham will take a five goal advantage into their second leg at White Hart Lane against Georgia's Dinamo Tbilisi, while Swansea City won 5-1 against Romania's Petrolul Ploiesti and should advance comfortably to the group stage.
Spanish side Sevilla will be confident of advancing to the group stage, holding a 4-1 lead over Poland's Slask Wroclaw.
The Poles nicked a shock lead in Sevilla before the home side pulled a goal back in the first half and then ran riot in the second stanza.
Sevilla's local rivals Real Betis welcome Czech Republic's Jablonec to the Estadio Benito.
Betis toiled hard for a 2-1 away win in the first leg and will be keen to bounce back against Jablonec after a 2-1 loss to Celta Vigo in La Liga on Sunday.
Stuttgart needs to overcome a 2-1 first-leg defeat in Croatia against Rijeka to advance to the group stage.
The Bundesliga club were hit by two late Rijeka goals to be 2-0 down before Vedad Ibisevic's 89th minute away goal salvaged a situation that was looking dire.
Other German representatives Eintracht Frankfurt are much more comfortable in their tie against Azerbaijan's Qarabag with two away goals in the bag before the second leg at home.
Stefan Aigner assisted both of Alex Meier's two goals in Azerbaijan in a 2-0 victory.
Dutch side AZ Alkmaar should have no issues advancing after a 3-1 first-leg win in Greece against Atromitos Athens.
The Greeks have not won any of their past six games and are expected to struggle in the second leg at the AFAS Stadion.
It is a different story for other Eredivisie team Feyenoord, who were beaten 1-0 by Kuban Krasnodar in the opening battle in Russia.
The Dutch giants snapped a four game losing streak with their 3-1 triumph over NAC Breda in their domestic league and will be hoping that form continues against the Russians.
In other second-leg ties,Russia's Rubin Kazan meet Norway's Molde having scored two away goals, France's St.Etienne must overcome a 4-3 defeat to Danish side Esbjerg and Cyproit team Apollon hold a 2-0 advantage over Ligue 1's Nice.