Given the scheduling implications brought on by the coronavirus pandemic, this match will be decided in Bulgaria on Thursday evening.
With his side having undergone a full pre-season programme, Jose Mourinho would have expected a strong performance when hosting a new-look Everton on Sunday afternoon.
However, while Spurs had their moments against the Toffees, they were arguably fortunate to only succumb by a 1-0 scoreline, leaving supporters pessimistic about their chances of cracking the top four.
While it is still early days, it has left the North London outfit under pressure ahead of a trip to Bulgaria, a visit which they earned through their efforts during the final weeks of the last campaign.
Although there are financial benefits from spending time on the European scene, Spurs face the prospect of taking on a relentless schedule, while also having to manage the conditions of players who may also represent their national teams a further six times this year.
At a time when Mourinho has openly criticised the fitness of his players, Plovdiv have no such concerns, having played 17 competitive matches since the beginning of June.
Although they only sit in sixth position in Bulgaria's top flight, Bruno Akrapovic will feel that the greater match time gives his side an edge over their high-profile foes.
Plovdiv have won four of their last five matches in all competitions, only losing out to regular European participants Ludgorets Razgrad.
The Railwaymen reached this stage of the tournament by overcoming Montenegrin outfit Iskra by a 1-0 scoreline late last month.
Lokomotiv Plovdiv Europa League form: W
Lokomotiv Plovdiv form (all competitions): LWWWWL
Tottenham Hotspur form (all competitions): L
Mourinho will try to strike a balance between rotation and still naming an experienced lineup, one which will likely include Harry Kane.
As for Plovdiv, Akrapovic may opt to stick with the same XI which pushed Ludogorets at the weekend before eventually losing out 3-1.
Forward Dimitar Iliev, who netted 12 times last season, scored the decisive goal in the previous round.
Lokomotiv Plovdiv possible starting lineup:
Lukov; Petrovic, Almeida, Masoero, Tsvetanov, Vitanov, Salinas, Iliev, Karagaren, Aralica, Ilic
Tottenham Hotspur possible starting lineup:
Hart; Aurier, Dier, Sanchez, Davies; Ndombele, Sissoko; Bergwijn, Alli, Lamela; Kane
We say: Lokomotiv Plovdiv 1-4 Tottenham Hotspur
Given the upcoming schedule, it remains to be seen how Mourinho will manage the fitness of his squad. However, regardless of whom the Portuguese selects on Thursday evening, it would come as a surprise if the North London outfit do not prevail in comfortable fashion.