Having arrived in Australia unvaccinated 12 months ago, the nine-times Melbourne champion was deported amid a backlash from angry Australians who had endured some of the world's toughest lockdowns as COVID-19 infections surged.
Nadal pounced on the opportunity, vanquishing Daniil Medvedev in an epic final to capture his second title at Melbourne Park, and more importantly his 21st at Grand Slams, before adding one more major trophy to his tally at the French Open.
While Roland Garros has been Nadal's domain for nearly two decades, Melbourne Park is almost as much for Djokovic, with the world number five capturing nine titles and holding an 82-6 record since 2007.
Djokovic has also proven to be unbeatable in Australian Open semi-finals and finals with 9-0 records in both, making him the automatic favourite anytime he enjoys a deep run.
Back in Australia after his three-year visa ban was waived, Djokovic has slowly won over fans and he soaked up the adulation en route to the Adelaide title -- his 11th trophy in the country -- but a more hostile reception could await in Melbourne.
If the seedings hold, Djokovic would not lock horns with Nadal until the final but he could take on Nick Kyrgios in a blockbuster rematch of last year's Wimbledon final, when the Serb won his 21st major.
Nadal's hopes of staying ahead of Djokovic will hinge on his recovery from an injury-plagued end to last year and a slow start to this season.
The top seed faces an early test of his fitness against British young gun Jack Draper with likely clashes against Frances Tiafoe and Medvedev lying ahead.
Second seed Casper Ruud made the most of Djokovic's enforced absence at the U.S. Open by reaching his second Grand Slam final of 2022 and the Norwegian will continue to knock on the door in search of his maiden major.
But the 24-year-old could run into fellow contenders Matteo Berrettini, Taylor Fritz, Alexander Zverev as well as Britain's former world number one Andy Murray who returns to the scene of his five Grand Slam runner-up finishes.
The injury withdrawal of world number one and U.S. Open champion Carlos Alcaraz robbed the year's first Grand Slam of a genuine title contender.
There is depth at the top of men's tennis and the likes of Medvedev, third seed Stefanos Tsitsipas and sixth seed Felix Auger-Aliassime could all step up to loosen the old guard's Grand Slam grip.