The pair convene at the Philips Stadion in perhaps the most high-profile tie of the round, with the team which comes out on top set to meet either Celtic or Midtjylland in August's third round.
Though many PSV fans have spent the past few weeks occupied by their club's weakening efforts to retain two stars of the Netherlands' Euro 2020 squad, the time has come for the Eindhoven outfit to embark on this year's European campaign.
While the immediate futures of fearsome full-back Denzel Dumfries and former Arsenal academy prospect Donyell Malen remain in serious doubt, coach Roger Schmidt must focus minds on a return to competitive action, following a series of straightforward friendly wins.
In pre-season, the Eredivisie club have swept aside modest RWDM and Delbrucker before drawing with Osnabruck and then beating PAOK 1-0 last Wednesday. Though it rarely pays to read too much into such warm-ups, PSV were impressive against the Greek side despite the narrow margin of victory - firing in 26 shots to the visitors' two, while keeping hold of the ball for most of the match.
As the Dutch giants make their return to the Champions League after missing out entirely last year - and previously being knocked out by Basel in the 2019-20 qualifiers - they have extended an unbeaten streak to 11 matches in all; including the final weeks of last season.
Leading the way in carrying out Schmidt's customarily attacking style, former Tottenham Hotspur youth team captain Noni Madueke, Israeli striker Eran Zahavi and last summer's surprise signing, 2014 World Cup-winner Mario Gotze, can create and score plenty of goals, with Malen not expected to return following his post-Euros break.
The 1988 European champions made it to at least the group stage on three occasions between 2015 and 2018 but have not been back at Europe's top table since. More accustomed to life in the Europa League of late, PSV will be determined to make the most of home advantage on Wednesday, as they seek to avoid that fate this year.
As one of the continent's most raucously supported sides, Galatasaray's recent absence from the Champions League has coincided with the advent of behind-closed-doors games across the globe.
With their last taste of group phase action coming in 2019 - when they failed to reach the last 16 from a group also featuring heavyweights Real Madrid and PSG - veteran coach Fatih Terim will now seek to replicate the Istanbul club's runs into the springtime of both 2013 and 2014, as fans finally return to stadiums.
Finishing second in the Super Lig last term, behind bitter rivals Besiktas only on goal difference, they approach this week's away leg on the back of a pair of pre-season wins. However, having beaten both Dinamo Bucharest and Kasimpasa in recent weeks, Gala's most recent practice fixture was called off in acrimonious circumstances last Tuesday.
A friendly match with Olympiakos was hastily cancelled, as club officials apparently refused to comply with Greece's strict COVID-19 testing regime. Told they would have to undergo new rapid tests in Athens despite bringing pre-flight results with them from the Turkish capital, Gala headed for home and an ill-tempered diplomatic row soon ensued.
Turkey's Foreign Minister went on to speak about the "suffering" of Terim's squad and that a "blockade" had prevented them from fulfilling the fixture. Despite the club now demanding an apology for "violation of human rights", the former Milan coach must quickly re-focus minds on the task at hand on Wednesday.
Currently linked with a whole host of transfer targets from across the European game, inching closer to a Champions League return this week could also boost Galatasaray's credibility as a desirable destination for ambitious players worldwide.
PSV coach Roger Schmidt has strengthened his defensive options during the summer, as Andre Ramalho signed a three-year deal after leaving RB Salzburg on a free transfer. Now set to play under Schmidt for a third time - having previously done so at both Salzburg and Bayer Leverkusen - the Brazilian centre-back is expected to pip veteran Nick Viergever to a place in the hosts' back four.
In the continued absence of Denzel Dumfries and Donyell Malen, it is thought that Schmidt will opt for another new signing, Phillipp Mwene, to replace the former, while Eran Zahavi should move into a more central position to fill the gap left by the latter.
While the midfield unit which started in the two most recent friendlies should be retained, Mohamed Ihattaren and New Zealand international Ryan Thomas provide alternatives who may feature in the second half.
Following their ill-fated - and short-lived - trip to Greece, two unidentified Galatasaray players tested positive for COVID-19, with the pair now isolating and set to miss both legs of this tie. Fatih Terim may therefore be forced to shuffle his pack slightly, but could otherwise name a similar lineup to the XI which started versus Dinamo Bucharest.
Former Monaco striker Radamel Falcao - who has great pedigree in European tournaments - is in competition with Ogulcan Caglayan for a start up front, with two other experienced campaigners, Arda Turan and Ryan Babel, expected to feature too.
PSV Eindhoven possible starting lineup:
Drommel; Mwene, Ramalho, Boscagli, Max; Van Ginkel, Sangare; Madueke, Gotze, Vertessen; Zahavi.
Galatasaray possible starting lineup:
Balaban; Yedlin, Luyindama, Ozturk, Bayram; Kara; Feghouli, Kilinc, Turan, Babel; Caglayan
We say: PSV Eindhoven 3-1 Galatasaray
Goals are almost assured at the Philips Stadion on Wednesday, as PSV only know one way to approach the game and should target a decisive first-leg lead to take to the banks of the Bosphorous.
The hosts have won four of their previous six meetings with Galatasaray, with no draws yet recorded between the two - a trend which is set to continue this time around.