Inter Milan begins the UEFA Europa League group stage with a tough test at in-form Dnipro, while defending champion Sevilla hosts Feyenoord.
Inter - unbeaten and having kept clean sheets in all four of its competitive contests so far this season - heads to Ukraine for its 350th European match fresh from a 7-0 thrashing of Sassuolo in Serie A.
It will be expected to be among the leading contenders for Europe's second-tier competition this season, but faces a Dnipro side which is also thriving.
Saturday’s admirable 5-2 win at Metalist in the Ukrainian Premier League took it to seven games undefeated in all competitions.
Portuguese playmaker Bruno Gama netted a treble in Kharkiv, while talisman Yevhen Konoplyanka marked his return from injury by coming off the bench to score an assist and a goal.
"We know we will play a formidable team who are internationally feared and respected," said Gama when asked about the challenge next up of facing the Italian giant in the Group F opener.
"It will be difficult, but if we play like we have been in the league we can do it."
Another side hoping to avoid an upset is Sevilla, which begins its title defence by hosting Feyenoord.
Tricky winger Aleix Vidal and prolific striker Carlos Bacca have helped the Spanish club make a flying start to 2014-2015.
Feyenoord, by contrast, is winless in four Eredivisie matches, and has lost five and drawn one of its past six Europa League outings.
Standard Liege, which are expected to battle with Feyenoord for the runners-up spot in Group G, starts out at home to Rijeka while outsider Qarabag welcomes Saint-Etienne to Azerbaijan in Group F’s other fixture.
Fiorentina, Napoli and Torino are also hoping to become the first Italian team since Parma in 1999 to conquer the Europa League.
The Florentine outfit is at home to French side Guingamp, with PAOK hosting Dinamo Minsk in Group K's other game.
Napoli will strive to put a difficult start to 2014-2015 behind it at home to Sparta Prague, with Young Boys and Slovan Bratislava also competing in Group I.
Torino, which has struggled for goals since the departures of Alessio Cerci and Ciro Immobile, is away to Club Brugge, as group rival Copenhagen and HJK meet in a Scandinavian affair.
Mauricio Pochettino is likely to rotate his Tottenham squad in Belgrade, with Andros Townsend and Harry Kane among those expected to start.
Besiktas versus Asteras is the other game in Group C.
Group H is arguably the most wide open. Everton entertains Wolfsburg, which has failed to win in four competitive matches this season, while Krasnodar visits Lille.
Group L is another unpredictable pool with Metalist and Legia Warsaw at home to Trabzonspor and Lokeren respectively.
Group J favourite Dynamo Kiev faces Rio Ave in Portugal and Steaua Bucharest hosts Aalborg.
Group E offers up PSV-Estoril and Panathinaikos against Dinamo Moscow.
Red Bull Salzburg open its Group D challenge against Celtic, the Scottish champion having dropped down to the Europa League after two unsuccessful attempts in the Champions League, having been reinstated after Legia Warsaw's exclusion for fielding an ineligible player.
Dinamo Zagreb faces Astra, while Borussia Monchengladbach hosts Villarreal in a match between Group A's favourites.
Zurich is away to Apollon Limassol in the pool's remaining fixture.