Djokovic won last year's Rome Masters title and will seek to do so again after topping Roger Federer 6-2, 7-6 (7-4) in one of Saturday's semifinals.
The current world No. 1 bested the former in 99 minutes, improving to 10-14 versus Federer en route to the finals berth, when he'll seek his 31st career title.
Nadal, meanwhile dispatched David Ferrer 7-6 (8-6), 6-0.
The Spaniard, who has won five of the last seven Italian Opens, dominated the second set by winning 72 percent of total service points to 37 percent for Ferrer.
Although losing to the Serb last year, Nadal also defeated Djokovic for one of his five Italian Open titles in 2009.