While the Russian enters the high-profile ATP 1000 event as the top seed, the draw is packed with stars. For one, there's 22-time grand slam winner Rafael Nadal, while young pretenders Stefano Tsitsipas, Casper Ruud and Carlos Alcaraz lurk in his vast shadow.
Medvedev has had a checkered build-up to the US Open on the hard courts, winning an ATP 250 title in Los Cabos, but falling to an inspired Nick Kyrgios at the first hurdle at the ATP Masters 1000 in Montreal last week.
"Talking about the match with Nick, I played good," reflected the pragmatic 26-year-old on atptour.com.
"I lost the match, so the result was, let's put it this way, terrible losing first round, if we don't talk about who I lost and which match. But because of… the last years and the way I'm feeling right now, I'm feeling confident for Cincinnati and [the] US Open itself."
Medvedev faces Dutchman Botic van de Zandschulp in the opening round on Tuesday, but knows the action will hot up soon after that. If all hold seed, he's on track to face fellow countryman and world number seven Andrey Rublev as early as the quarterfinals.
"For sure [I] want to try to win as many matches as possible here to grow this confidence of winning matches for the US Open," continued Medvedev.
"But we'll take it match by match. As we see in the draw, I feel that the draw is very, very packed. Sometimes you have somebody retiring here and there, somebody tired from the season, maybe not in the best shape here. When I look at the draw I'm like wow, every match we have, even in the first round, is a tough match."