Diego Alonso's team ran out 2-1 winners on home soil in the opening encounter last week, but they now head to hostile territory at Stadion Hristo Botev on Thursday night.
Match preview
Picking up where they left off at the end of the 2023-24 domestic campaign - as well as keeping the momentum going from back-to-back friendly successes over AEK Larnaca and Maccabi Netanya earlier this month - Panathinaikos were two goals up by the time the half-time whistle blew last week.
Two of the experienced heads in the team - 30-year-old Swedish striker Alexander Jeremejeff and 31-year-old Greek playmaker Anastasios Bakasetas - were on target, the latter striking from the spot, before Alen Korosec cut the Athens arrears in half at the Olympic Stadium.
Despite that 71st-minute scare, Panathinaikos clung on to take a slender advantage to Bulgaria, in what will be head coach Alonso's first competitive away game in charge of the Greek powerhouses; last week's first leg was his Shamrock baptism following his summer arrival.
Formerly of Inter Miami, Uruguay and most recently Sevilla - a spell that is best consigned to the back pages of his personal annals - Alonso endeavours to maintain his perfect start to life in the Panathinaikos hotseat while avoiding unwanted history for the visitors.
Indeed, Panathinaikos have never suffered a second-round exit in Europa League qualifying and came within 180 minutes of the Champions League group stage last year, only to fall to Braga's superiority and then fail to make it out of their second-tier UEFA group.
Panathinaikos' European pedigree is still far superior to that of hosts Botev Plovdiv, who were UEFA Cup first-round regulars back in the 1980s and 1990s but are yet to reach the Europa League proper, falling in qualifying three times down the years.
In fact, should the Bulgarian outfit overturn their 2-1 deficit and send Panathinaikos packing on Thursday, they will match their best-ever Europa League result, having never gone past the third round of the preliminary competition, bowing out at that point in 2013 and 2017.
Earning their spot in UEFA's second-tier competition thanks to their Bulgarian Cup triumph in 2023-24, the team led by Dusan Kerkez edged out Maribor 4-3 on aggregate in their first-round showdown to earn a date with Panathinaikos, who have not had domestic commitments to manage alongside their European affairs.
In contrast, Botev Plovdiv are already two games into their new Bulgarian First League campaign and have accrued an applaudable four points from the opening six on offer, sinking Botev Vratsa before drawing 2-2 with Lokomotiv Plovdiv at the weekend.
A trip to Krumovgrad comes just three days after Thursday's second leg for Kerkez's side, who are fighting for the right to meet either Serbian outfit Vojvodina or former European powerhouses Ajax in the penultimate preliminary round.
Botev Plovdiv Europa League form:
W
D
L
Botev Plovdiv form (all competitions):
Panathinaikos Europa League form:
W
Team News
No injury or suspension concerns arose for Panathinaikos in their triumphant opening tie, where a handful of notable new signings - including ex-Sheffield United defender George Baldock and former Getafe midfielder Nemanja Maksimovic - were on the bench.
However, erstwhile Leicester City winger Tete was not involved, having only arrived on a permanent deal from Galatasaray on the day of the game, but the Brazilian should be in line to make his debut in the second leg.
Tete could very well threaten Daniel Mancini's spot on the right-hand side in Alonso's 4-2-3-1 setup; the 27-year-old was the only Shamrock player to pick up a booking in the opening encounter.
Botev Plovdiv also emerged unscathed from the first leg on the physical front, although centre-back Atanas Chernev and striker Georgi Nikolov are both in the infirmary; the latter is facing several more weeks out with torn ligaments.
Following his arrival on a permanent deal from Inter Milan, 20-year-old attacker Nikola Iliev was only considered for a place on the bench in the first leg, but he started and scored the opener in the weekend's draw with Lokomotiv.
Iliev's spot in the first XI for Thursday's second leg therefore ought to be safe, so Christian Nwachukwu may have to accept a bit-part role on home turf.
Botev Plovdiv possible starting lineup:
Igonen; Ukaki, Tamm, Conte, Balogiannis; Perera, Eto'o; Akere, Popov, Iliev; Ujah
Panathinaikos possible starting lineup:
Dragowski; Vagiannidis, Schenkeveld, Jedvaj, Mladenovic; Vilhena, Arao; Tete, Bakasetas, Djuricic; Jeremejeff
We say: Botev Plovdiv 0-1 Panathinaikos (Panathinaikos win 3-1 on aggregate)
All five of Botev Plovdiv's competitive games so far this term have seen Kerkez's men both score and concede, but we can envisage that streak being snapped as their Europa League journey comes to an end.