Manchester United will come up against their former striker Robin van Persie after being drawn in a tough Europa League group alongside Fenerbahce, Feyenoord and Zorya Luhansk.
Three-times European champions United must negotiate a competitive group if they are to win one of the few titles that has eluded them.
The Premier League side will face 19-times Turkish champions Fenerbahce, who missed out on the Champions League group stage after a 4-3 aggregate defeat by AS Monaco in the third qualifying round.
They are managed by former Netherlands coach Dick Advocaat and include ex-United forward Van Persie who began his career with Feyenoord.
The Dutch Cup holders finished third in the Eredivisie last season. Zorya qualified as Ukraine's fourth-placed team.
Frank de Boer's Inter side have been drawn against English side Southampton as well as Sparta Prague and Israel's Hapoel Be'er Sheva, who gave Celtic a scare in their Champions League qualifier.
After missing out on Champions League football, AS Roma will have to console themselves by playing Czech side Viktoria Plzen, Austria's Austria Vienna and Romanian side Astra Giurgiu.
Villarreal, beaten semi-finalists last season, meet former European champions Steaua Bucharest, FC Zurich and Osmanlispor.
Group-stage first-timers Dundalk of Ireland meet AZ Alkmaar, Maccabi Tel Aviv and Zenit St. Petersburg, who reached the Champions League round of 16 last season.
The top two teams from each of the 12 groups advance to the round of 32 where they will be joined by the eight third-placed teams from the Champions League group stage.
The groups in full:
GROUP A Manchester United Fenerbahce Feyenoord Zorya Luhansk
GROUP B Olympiakos Piraeus Apoel Nicosia Young Boys Astana
GROUP C Anderlecht St Etienne Mainz Qabala GROUP D Zenit Saint Petersburg AZ Alkmaar Maccabi Tel Aviv Dundalk
GROUP D Zenit Saint Petersburg AZ Alkmaar Maccabi Tel Aviv Dundalk
GROUP E Viktoria Plzen AS Roma Austria Vienna Astra Giurgiu
GROUP F Athletic Bilbao Genk Rapid Vienna Sassulo
GROUP G Ajax Amsterdam Standard Liege Celta Vigo Panathinaikos
GROUP H Shakhtar Donetsk Braga Gent Konyaspor
GROUP I Schalke 04 Salzburg Krasnodar Nice
GROUP J Fiorentina PAOK Slovan Liberec Qarabag
GROUP K Inter Milan Sparta Prague Southampton Hapoel Be'er Sheva
GROUP L Villarreal Steaua Bucharest Zurich Osmanlispor