This knockout edition of the New York Derby is also a clash between the current top two teams on the Eastern Conference table, with defending MLS Cup champions NYCFC in first place with 27 points from 14 matches, one ahead of RBNY's pace of 26 points from 16 matches.
As such, RBNY head coach Gerhard Struber feels a proving ground awaits.
"I think this is a big test, a big chance to grow," Struber said. "My whole team has the chance to play against the best team in the league, or one of the best teams in the league. For us, it's always a chance to grow and show at the same time what we can do. We believe that we can win tomorrow. We have the clear goal to go to the next round."
Struber said his starting XI will be assembled accordingly, despite fixture congestion that has the midweek USOC clash sandwiched between two league matches. On top of that, the Austrian manager added the automatic 2023 Concacaf Champions League spot awarded to the USOC winner should be another motivating factor.
"Very important, [this is] a cup competition," Struber said. "My understanding from a cup competition, from Austria, from England, is always a chance of a title. This is our job. If we have a chance at a title we have to do everything from a professional side we can do [so] we can realize it. Tomorrow we have a chance to go to the next round and I expect from my players, my coaching staff, from everyone, and also from our supporters, that we have many supporters in the stadium. We need it tomorrow, they help us to go to the next round.
"We don't forget, we go directly to the Concacaf Champions League, maybe win the title. I think this is also an outstanding good chance, that young players go to an international competition. You can use different games on a different level and it's always a big chance that you have to do everything you realize in the end the best output."
Cushing's new groove
NYCFC enter amid a transition phase after former head coach Ronny Deila departed last week to lead Belgian first-division side Standard Liege. Assistant coach Nick Cushing has taken over on an interim basis.
While the news came as a surprise to the players, center back Alexander Callens believes the Cityzens have a strong enough foundation to maintain their top-of-the-table form that's continued from their 2021 MLS Cup title.
"All I know is that it surprised us all," the Peruvian international said. "It surprised me because I wasn’t here, I was on international duty. I found out in the morning of the same day that I had my World Cup Qualification game. It was a surprise to me because I thought he was happy, that all was good here, that he felt happy here.
"He had been here for two and a half years and the truth is that I didn’t understand it but everything happens for a reason, and I’m sure he’ll have plenty of new opportunities and experiences. I wish him the best. He’s a great manager and a great friend. Now on to Nick. Nick is familiar with us and we know how Nick works. The group will not change much."
Wednesday's match marks the third all-time USOC game between the rivals, with RBNY emerging victorious twice before in 2017 and 2018.
It sets up a lively scene at Red Bull Arena, where NYCFC's fanbase also figures to be well-represented for the New York Derby bout.
"It's different tomorrow," Struber said. "It's a knockout game, from the mental side it's a different game. We have to create the atmosphere, a cup atmosphere, a knockout atmosphere for New York City FC that we are ready – ready from the first second to go in this fight and go in the next round."
Other MLS quarterfinals
All Open Cup games will be streamed on ESPN+. Six of the eight teams left standing are from MLS.