The Big Apple tennis takeover returns Monday as the U.S. Open lures the sport’s biggest stars to Flushing Meadows for the two-week tournament.

The prestigious Grand Slam event is the last of four majors held each year.

Here’s a look at storylines to watch for through the Sept. 11 men’s final.

Scotsman vs. Djoker

Novak Djokovic and Andy Murray rank 1 and 2 in the world, respectively. It’s been two years since neither reached the men’s final at a Grand Slam — that occurred at the 2014 U.S. Open.

Serbia’s Djokovic, the defending U.S. Open champion, has won 24 of 34 career matchups between the two, including three of four this year. But Scotland’s Murray has momentum on his side after winning the second Wimbledon and Olympic tournaments of his career this summer.

The two tennis titans met in the final of the Australian Open and French Open this year, so it’s a smart bet they’ll square off again in two weeks.

Spoiler warning

While Djokovic and Murray are the unquestioned top two, men’s singles isn’t short on top-notch talent capable of winning it all.

No. 3 Stan Wawrinka of Switzerland is a two-time Grand Slam winner searching for his first championship in Queens, where he reached the semifinal last year. Spain’s Rafael Nadal, the No. 4 seed, hasn’t been in peak form since his last major victory in Paris two years ago, but there’s no counting out the 14-time Grand Slam winner.

One all-time great who won’t be in the mix is Roger Federer. The winner of 17 majors — the most ever in men’s singles — and five-time U.S. Open champion is done for the year due to a knee injury.

Chasing Serena

With one more Grand Slam title, Serena Williams will become the Open-era leader in major victories and break a tie with Steffi Graf at 22.

As always, top-ranked Williams is the favorite coming off a win at Wimbledon. But don’t award her a seventh U.S. Open crown just yet — even with Maria Sharapova away from the court due to PED suspension.

No. 2 Angelique Kerber of Germany topped Williams Down Under in January, and No. 3 Garbiñe Muguruza of Spain stunned Serena in the French final. Neither will be intimidated by the all-time great’s mystique.