Australia's world No.6, who lost in the final of one of his favourite hardcourt events to Carlos Alcaraz last year and Jannik Sinner the year before that, is this time favourite to make it third time lucky in the Netherlands.
But he'll have his hands full with Wawrinka, who not content with rolling back the years at his final Australian Open where he became the oldest man since Ken Rosewall to reach the third round, has now gone on to earn a remarkable 'generation game' triumph.
'Stan the man' had been expecting to play Australian stalwart Aleksandar Vukic in the last-32 in his latest farewell tour match on Wednesday but the Sydneysider scratched shortly before the match with injury, allowing 17-year-old lucky loser Thijs Boogaard a chance to play the three-time grand slam champ instead.
Wawrinka, who won the Rotterdam crown in 2015, downed the youngster 6-4 6-3 in a clash spanning more than two decades in age difference.
Indeed, the 23 years and three months separating the pair made this the second-largest age gap in ATP Tour history, trailing only Dominic Thiem's win over Thomas Muster - 25 years 11 months - Vienna in 2011.
Next up is de Minaur, who outplayed Wawrinka on the clay of Monte Carlo in their only clash two years ago.
"He's a tough player," Wawrinka conceded.
"Especially in these conditions, it's going to be difficult to generate something. But I'm looking forward to the challenge. I've been playing some good matches against top players, so I'm always trying to push myself."
De Minaur isn't the only Australian with an eye on the prize, though. Unsung Chris O'Connell earned a notable last-16 victory against Britain's former Wimbledon semi-finalist Cam Norrie, 7-6 (11-9) 6-4, to book a quarter-final date on Friday with dangerous French left-hander Ugo Humbert or Dutch wildcard Guy Den Ouden.
The 31-year-old O'Connell had come into the tournament off the back of five straight defeats including a first-round, five-set exit at Melbourne Park, but has now won four matches in five days, including two qualifiers, which will thrust him back into the world's top-100 next week from his current ranking of 119.
There was disappointment, though, for a third Sydneysider Alexei Popyrin, who was beaten 7-5 6-3 by in-form Canadian No.2 seed Felix Auger-Aliassime, who won the Montpellier Open last weekend and is scheduled to meet de Minaur in the Dutch final.
At the hardcourt indoor event in Dallas, Australian duo James Duckworth and Adam Walton both suffered opening-round straight-sets defeats.
World No.83 Duckworth lost 6-2 6-4 to American Eliot Spizzirri, while 93-ranked Walton was beaten 6-4 6-2 by French veteran Adrian Mannarino.
The last Aussie hope at the women's Qatar Open in Doha, Daria Kasatkina, trying to recover her old form and confidence having dropped to No.61 in the world, had a great start in her last-16 duel with world No.2 Â Iga Swiatek before Poland's Wimbledon champ outplayed her 5-7 6-1 6-1.
