The Scottish side trail 1-0 following last week's first leg, having succumbed to a stoppage-time goal after holding firm for 90 minutes.
Match preview
Continuing their wretched start to the new season, Hearts lost out to virtually the last kick of the game in Plzen, as substitute Daniel Oyegoke turned a cross into his own net to hand the home side victory.
The Jambos therefore return to Tynecastle with a deficit to overturn, and failure would see them drop down into the third-tier Conference League.
Form is certainly not on their side, as after concluding an otherwise successful 2023-24 campaign by winning just one of their last six matches, Steven Naismith's men have started very slowly this season.
Sunday's 3-1 defeat against Motherwell sees them sitting 10th in the very early Scottish Premiership standings, and they have scored only twice across all competitions so far.
Hearts have taken just one point from three league games - also losing both their first continental contest and to Falkirk in the League Cup - piling pressure on Naismith to turn things around.
Making their first appearance in Europe since reaching the Conference League two years ago, the Jambos may be bound for the same competition again this term, barring a spirited fightback on Thursday.
Viktoria Plzen start favourites to get their name into Friday's Europa League draw, though they may feel their advantage heading into the second leg should be greater, having had 18 goal attempts last week - only three were on target.
By contrast with Hearts - who also finished third in their domestic league last season - the Czech side have got off to a rapid start in 2024-25, starting with four wins and one draw.
A recent 3-0 victory over Ceske Budejovice makes Miroslav Koubek's men the closest challengers to First League leaders Sparta Prague, and an unbeaten start extends to UEFA qualifying, having previously overcome Kryvbas in their opening Europa League qualifier.
Plzen's weekend league fixture was postponed to boost hopes of thriving in Europe, which the six-time Czech champions certainly did last term: after taking maximum points from their Conference League group, they went out in the quarter-finals to eventual finalists Fiorentina.
With a record of six clean sheets from eight games so far this season - including an ongoing streak of four - they will now expect to defend their first-leg advantage in Scotland.
Hearts Europa League form:
L
Hearts form (all competitions):
Viktoria Plzen Europa League form:
W
W
W
Viktoria Plzen form (all competitions):
D
W
W
W
W
W
Team News
Amid a busy schedule - and on the back of a losing run - Hearts may make changes on Thursday evening, but as Zander Clark is still sidelined with a back injury, veteran goalkeeper Craig Gordon will continue between the posts.
The 41-year-old made his 23rd European appearance for the Jambos last week, surpassing a previous club record, and he should start behind a back three at Tynecastle.
Meanwhile, captain Lawrence Shankland is often accompanied up front by Kenneth Vargas, but Yan Dhanda or Yutaro Oda could beat the latter to selection.
Alongside Clark, Beni Baningime and Calem Nieuwenhof will both miss out for the hosts due to injury, while Christophe Kabongo, Cheick Souare, Jan Sykora and Lukas Hejda all feature on a long list of Plzen absentees.
Furthermore, star centre-back Robin Hranac has just agreed a move to Hoffenheim, so Miroslav Koubek must make a change to his preferred three-man defence.
Viktoria's top scorer in qualifying so far is Daniel Vasulin, with two goals in the previous round, and he should start again; experienced striker Matej Vydra is most likely to feature from the bench.
Hearts possible starting lineup:
Gordon; Kent, Kingsley, Rowles; Taylor, Devlin, Boateng, Grant, Salazar; Vargas, Shankland
Viktoria Plzen possible starting lineup:
Tvrdon; Dweh, Sene, Jemelka; Kopic, Cerv, Kalvach, Sulc, Havel; Jirka, Vasulin
We say: Hearts 1-1 Viktoria Plzen (Viktoria Plzen win 2-1 on aggregate)
The combination of a tight Plzen defence - albeit now missing its strongest component - and Hearts' attacking woes suggests that the Czech side will prevail.