Nadal, back on top of the world rankings for the first time in three years, is a two-time winner in New York, his 2010...
Nadal, back on top of the world rankings for the first time in three years, is a two-time winner in New York, his 2010 and 2013 titles forming part of his 15-Slam portfolio which was embellished by a record 10th French Open in June.
Federer, the five-time US champion from 2004-2008, is bidding for a 20th major and third of the year after capturing the Australian Open and Wimbledon titles.
Victory in the men's final on September 10 would also make the 36-year-old the oldest US Open champion of the modern era and oldest overall since Bill Tilden in 1929.
The path to the title for Nadal and Federer has been eased by the removal of two-time champion Novak Djokovic, the former world number one who has shut down his season to recover from an elbow injury.
Also out of the way is defending champion Stan Wawrinka, another long-term casualty who is facing knee surgery.
Add into the mix the ongoing hip problems of 2012 champion Andy Murray, and all the indications point to a tournament where the sport's two most durable warriors are likely to be amongst the last men standing.
Not that they are getting carried away by their prospects.
Nadal, 31, heads to New York on the back of a quarter-final loss to Nick Kyrgios in Cincinnati and a Montreal last-16 defeat to Canadian teenager Denis Shapovalov.
"New York is a completely different event," said Nadal, who has not got past the fourth round at the US Open since 2013.
"Different ball and in the history of my career in New York I played much better.
"I believe that I did the things well enough during the whole year to be ready to compete at the highest level in New York."
Federer, meanwhile, is looking to move beyond Pete Sampras and Jimmy Connors by claiming a sixth US Open and reach a first final in the city since his sensational 2009 loss to Juan Martin del Potro.
His record-blazing eighth Wimbledon title in July was followed by a Montreal final defeat to Alexander Zverev and a pull-out from Cincinnati with a back injury.
But with a 2017 record of five titles, 35 match wins and just three losses, the evergreen Swiss remains the sentimental favourite.
"Winning my third of the year, my 20th Grand Slam, would be completely insane. I just hope I'm going to be 100% ready when the moment arises," said Federer who missed the 2016 US Open to rest a knee injury.
When Murray stunned Djokovic to win the 2012 title, he became the first British man to lift a Slam singles title in 76 years.
A hip injury contributed to a quarter-final exit at Wimbledon and he has been sidelined since, although he made the trip to New York and expects to play.
With Djokovic, Wawrinka, as well as 2014 runner-up Kei Nishikori out of action, the tournament should also present the perfect opportunity for the widely-touted 'NextGen' to step up.
Alexander Zverev, the world number six, downed Federer for the Montreal title but slumped first time out in Cincinnati to US teenager Frances Tiafoe.
Zverev has never got beyond the fourth round of a Slam and was a second round loser in New York in 2016.
Kyrgios, the runner-up in Cincinnati, made the quarter-finals at the Australian Open in 2015 and Wimbledon in 2014 but his US Open best is a run to the third round.
World number eight Dominic Thiem, a semi-finalist at Roland Garros in 2016 and 2017, has never got beyond the last 16 in New York.