The Madrid Open gets underway on Monday and both stars have been handed tough routes to glory.
But it is No 10 seed Djokovic who who has been once again handed a nightmare half.
Nadal has been drawn in the opposite half to his Serbian counterpart so they cannot meet until the final.
The world No 1, who is handed a first-round bye, will face a possible second-round clash with Gael Monfils.
Croatia’s Borna Coric could await in the third round with a potential quarter-final meeting against Dominic Thiem – tipped by many to be Nadal’s heir on clay.
In-form Juan Martin del Potro is likely to meet the Spaniard in the semi-final.
Meanwhile, Djokovic will get underway against Monte Carlo Masters runner-up Kei Nishikori – by far the tie of the first round.
British No 1 Kyle Edmund is expected to face the winner in round two, with David Goffin a potential third-round opponent.
Gregor Dimitrov then would await in the last eight before a semi-final showdown with Barcelona Open runner-up Stefano Tsitsipas.
A daunting week awaits Djokovic but this could be the perfect opportunity to finally put his recent injury nightmare behind him.
However, Nadal has to remain the clear favourite to win the competition for the sixth time in his career.
The 31-year-old has not dropped a set on clay in 12 months as he took his Open Era record up to 46 last week.
Nadal potential Madrid Open route
R1: Bye
R2: Monfils
R3: Coric
QF: Thiem
SF: Del Potro
F: Djokovic
