The 20-year-old Spaniard, who has won a record 60 matches on the slow surface, will need to see off a very competitive field if he is to retain his title in the principality.
World number one Roger Federer, who lost to Nadal in last year's French Open final, leads the competition with Argentine Guillermo Canas a potential threat to the Spaniard.
The usually dominant Swiss stumbled to two surprise defeats by Canas at the Indian Wells and Miami Masters Series.
Monte Carlo Masters
Nadal claims first serve the key
22/04/2007 AT 17:17
However, Federer recently said the last defeat against the Argentine gave him a break he spent building up his physical condition, one of the keys to claycourt success.
"It's exactly what I didn't have for the last two or three years, one of those surprise losses where all of a sudden I got more time off so I hope it can help me out," Federer told a press conference in Basel last week.
The Swiss, who has 10 grand slam titles to his name but has never won the French Open, has not played competitive tennis since his last defeat.
Nadal, who won the Indian Wells event before bowing out to Serbian Novak Djokovic in the quarter-finals in Miami, vowed to play at his best level in Monte Carlo.
"I will try to have a good result and to play my best tennis and that's it," he told his personal website.
"If I play my best tennis, I'm going to have a chance to have a good claycourt season.
"If not, I won't have a good clay season. But that's the thing. I will just try to play my best," said Nadal, who beat Federer in last year's final.
Nadal's last defeat on clay was against Russian Igor Andreev in April 2005 in the quarter-finals of the Valencia Open.
Organisers will be hoping for a spectacular tournament after lodging a complaint against the ATP following the ruling body's decision to drop Monte Carlo from the Masters Series.
Monte Carlo Masters
Fed: Rafa forces me to improve
22/04/2007 AT 16:39
Monte Carlo Masters
Nadal wins third Monte Carlo title
22/04/2007 AT 12:17