But world number two Novak Djokovic is out, the suffering Serb an apparent victim of the breathing problems which forced him to quit a quarter-final at his home Serbia Open on Friday.
Holder Federer and Nadal played the final a year ago at the Caja Magica, where a movable roofs over showcourts look likely to be useful with rain predicted for some of the upcoming week.
World number one Federer kick-started what proved to be a career-defining run to a first French Open crown, initiated when he beat Nadal for the title a year ago.
With the Swiss stalled in Estoril, Portugal, by rain at the semi-final stage, Nadal has had the week off as the four-time French Open winner finally starts to plan his playing schedule with time built in for the rest needed by his fragile knees.
The second-seeded Spaniard should come in fresh after claiming a fifth Rome title a week ago with a win over David Ferrer.
With his preferred clay season in full bloom, Nadal is happy to be on court, with two titles from two events so far this spring prior to the last major tune-up in the Spanish capital.
"I need high motivation to keep winning," said the world number three. "The important thing is to have enough motivation to want to improve all the time -- this is the main thing for me.
"For about eight months or longer (11 months between May, 2009. in Rome and Monte Carlo in April), I didn't win a tournament. then I won two.
"Every time I go on court I try my best and I try to do this all the time."
Third seed Andy Murray will try and improve a luckless clay start, with the Scot posting one win from three matches so far.
Fourth-seeded French Open finalist Robin Soderling of Sweden, who lost in Paris to Federer, will try to surpass his Barcelona final of last month against Fernando Verdasco.
On the women's WTA side, Maria Sharapova makes her return to the game after last playing in mid-March at Indian Wells.
The 11th-seeded Russian has been dealing with injuries over the last few seasons and will be making her debut at the obligatory women's event with a first-round match against Lucie Safarova.
Top seed Serena Williams and her fourth-seeded sister Venus will need to recover from back-to-back losses this week in Rome to Serb Jelena Jankovic, the number seven in the Spanish capital.
Dane Caroline Wozniacki takes the second seeding and begins against a qualifier while Russians Svetlana Kuznetsova (fifth) and Elena Dementieva (sixth) will hope to make up ground during the French Open run-up after Rome disappointments.
Australian Samantha Stosur, the Charleston champion whose only loss on clay this season came in the Stuttgart final against Justine Henin, is seeded eighth after a week of rest.