The six-times Roland Garros champion has dropped only 10 games in three clay-court meetings against his fourth-round opponent Juan Monaco and he is on an 11-match winning streak against Argentine players.
Second seed Nadal, who has yet to drop a set this year, is scheduled on Court Suzanne Lenglen, where he stands undefeated since his French Open debut in 2005.
Russian second seed Maria Sharapova will continue her bid for the only grand-slam title missing from her collection when she faces the unseeded Czech Klara Zakopalova.
If she reaches the final in Paris for the first time, she will take over as world number one after top seed Victoria Azarenka of Belarus was knocked out in the fourth round on Sunday.
France fans will be cheering for 17th seed Richard Gasquet, who has been in impressive form so far, when he entertains British world number four Andy Murray, whom he beat in their last meeting in the Rome Masters.
Defending champion Li Na of China, who survived the loss of the first set in her previous match, will start as hot favourite against unheralded Kazakh Yaroslava Shvedova.