After finishing second in Group B, Anderlecht had to come through the playoffs to reach the last 16, while Villarreal booked their place in the knockout phase by winning Group C.
Match preview
Having made it through two qualifying rounds to reach the competition proper, Anderlecht won just two of their six group games, recording two draws and two losses to finish 10 points behind Group B winners West Ham United.
Anderlecht's unconvincing Europa Conference League campaign continued with a 1-0 defeat at Ludogorets in the knockout playoffs, but they managed to turn the tie around with a 2-1 victory before advancing via penalties.
In fairness, Felice Mazzu's men dominated the second leg, racking up 20 shots while enjoying the lion's share of possession on home soil, before a 3-0 penalty shootout triumph sealed the deal for the Brussels outfit.
Since then, Anderlecht have taken one point from a possible six in the Belgian Pro League, with a 2-2 draw against Standard Liege preceding a 1-0 defeat at Gent, leaving Mazzu's side all the way down in 10th place in the table.
Having lost 12 of their 28 league matches this season - picking up 10 wins and six draws in the process - the 34-time Belgian champions are 31 points shy of first-placed Genk and on course to record their lowest league finish in decades.
By contrast, Villarreal are enjoying another impressive campaign both domestically and on their European travels, as they find themselves sixth in the La Liga table and among the favourites to win the Conference League.
The Yellow Submarine coasted to a comfortable Group C triumph earlier in the season, suffering a solitary defeat in six matches to finish four points clear of second-placed Lech Poznan, while no team scored more group-stage goals than Villarreal's 14.
A four-game losing streak in La Liga across January and February threatened to derail Villarreal's campaign, but Quique Setien's men have returned to winning ways in recent weeks, securing back-to-back victories to steady the ship.
After scoring in each of the last three La Liga games, Jose Luis Morales will be confident of adding to his four Conference League goals on Thursday, while Samuel Chukwueze is also in fine form, having bagged two goals and three assists in his previous three appearances.
Chukwueze has now registered 10 goals and 10 assists in all competitions this season, while Alex Baena and Gerard Moreno have both notched 10 goals and five assists, highlighting Villarreal's attacking firepower.
Anderlecht Europa Conference League form:
L
L
D
W
L
W
Anderlecht form (all competitions):
W
L
D
W
D
L
Villarreal Europa Conference League form:
W
W
W
W
D
L
Villarreal form (all competitions):
L
L
L
L
W
W
Team News
Anderlecht will be without two key players for the first leg, as defender Hannes Delcroix (knee) and midfielder Marco Kana (toe) are both sidelined due to injury.
Veteran centre-back Jan Vertonghen will continue to captain the side, with the 35-year-old likely to be joined by teenager Zeno Debast in the host's backline.
Yari Verschaeren has chalked up two goals and two assists in the Conference League this term, so the 21-year-old attacking midfielder is expected to offer support to striker Islam Slimani on Thursday.
As for Villarreal, they will be without Francis Coquelin for the remainder of the campaign after the former Arsenal midfielder sustained an ACL tear against Barcelona last month.
Senegal forward Nicolas Jackson - who has bagged three goals and three assists this season - is also expected to miss the first leg, having been sidelined since January due to a hip problem.
Following a couple of injury setbacks, Gerard Moreno came off the bench to grab an assist in last weekend's 2-0 victory over Almeria, so the experienced striker is likely to feature on Thursday.
Anderlecht possible starting lineup:
Verbruggen; Murillo, Debast, Vertonghen, Sardella; Ashimeru, Diawara, Verschaeren; Dreyer, Slimani, Amuzu
Villarreal possible starting lineup:
Reina; Foyth, Albiol, Torres, Moreno; Terrats, Parejo, Baena; Chekwueze, Moreno, Pino