Whoever progresses from the fixture later this week will take on either Roma or Sevilla in the quarter-finals.
Despite being well-positioned to earn Europa League football next season through the Premier League, Wolves now find themselves in a situation where they must win the competition to earn a second successive year on the continent.
Three defeats from six matches resulted in Nuno Espirito Santo's team dropping down to seventh position, which proved not enough for European qualification after Arsenal's FA Cup triumph.
Nuno and his players are now tasked with trying to negotiate a difficult draw to win this tournament, success which would earn the club a first ever spot in the Champions League.
Based on their most recent efforts in pivotal matches, that appears unlikely at this stage, but Wolves have shown in the past that they are capable of responding to adversity.
At a time when he is being linked with a big money elsewhere, Raul Jimenez will hope to improve on a run of just two goals from his last seven outings.
While Wolves are currently enduring a low point, Olympiacos are experiencing emotions on the opposite end of the scale having won the Greek top flight by 18 points.
Although there was disappointment after narrowly missing out on an unbeaten campaign through a last-minute goal to nearest challengers PAOK on July 12, Olympiacos responded with back-to-back 3-0 wins.
That would have reassured Pedro Martins that his players are in the right frame of mind ahead of a trip to England, their third such journey since November.
After pushing Tottenham Hotspur in the Champions League earlier in this season, Olympiacos recorded a famous win versus Arsenal at the Emirates Stadium in February.
Wolverhampton Wanderers Europa League form: WDWWLD
Wolverhampton Wanderers form (all competitions): LLWDWL
Olympiacos Europa League form: LWD
Olympiacos form (all competitions): WDWLWW
Having began the game against Chelsea among the replacements, Joao Moutinho will almost certainly be handed a recall.
With Wolves ahead on away goals, Nuno could opt to go with a 3-5-2 formation, resulting in Adama Traore beginning on the substitutes' bench.
Olympiacos will be without centre-back Ruben Semedo, who was sent off during the first half of the first leg.
Wolverhampton Wanderers possible starting lineup:
Patricio; Boly, Coady, Saiss; Doherty, Dendoncker, Moutinho, Neves, Jonny; Jota, Jimenez
Olympiacos possible starting lineup:
Sa; Elabdellaoui, Ba, Cisse, Tsimikas; Guilherme, Bouchalakis, Camara; Valbuena, El-Arabi, Masouras
We say: Wolverhampton Wanderers 2-1 Olympiacos
Having failed to qualify for next season's competition, there will be a few nerves within the Wolves side during this game. Nevertheless, they are due a response after their poor performance last time out, and we feel that they should just do enough to edge out Olympiacos on this occasion.