The Japanese came through a two-day marathon with rising Korean Hyeon Chung early on Sunday, prevailing 7-5, 6-4, 6-7(4), 0-6, 6-4 on Court 1 after rain had curtailed play on Saturday.
That gifted Verdasco an extra day of recuperation after he dispatched the Uruguayan Pablo Cuevas, 6-2, 6-1, 6-3, in blistering fashion.
The duo have met five times in their careers, with Nishikori holding a narrow 3-2 head-to-head record over the Spaniard.
Nishikori’s route to the last 16
It had been plain sailing for the 27-year-old until he met the talented Chung in the previous round.
He dropped the opening set against Thanasi Kokkinakis of Australia in round one, but he recovered to triumph 4-6, 6-1, 6-4, 6-4.
Frenchman Jeremy Chardy was then removed without too much of a fuss, bagelling the hometown hero in set two to move into the third round, 6-3, 6-0, 7-6(5).
Nishikori, however, required treatment on his shoulder in the third set, surrendering a double break advantage to Chardy who forced a tie-break.
The Japanese star has battled with injuries throughout his professional career but he told reporters after his victory that his shoulder did not cause him any discomfort after the rub down.
And when he raced out to a two sets-to-love lead against Chung on Saturday few could question the 27-year-old’s words.
Yet he lost the fourth set without winning a single game and we were treated to a rare sighting of racket abuse from the Japanese when he fell behind 3-0 in that set.
Rain quelled Chung’s momentum and Nishikori recovered in the deciding set.
Afterwards, he allayed any injury fears to reporters.
Verdasco’s route to the last 16
Verdasco, in contrast, kickstarted his Roland Garros campaign by ousting Italian Open champion Alexander Zverev in four sets.
Pierre-Huguest Herbert, more renowned for his doubles prowess, then pushed the Spaniard to a fifth set before he prevailed 6-3, 3-6, 4-6, 6-3, 6-3.
The 33-year-old then squared off against Cuevas, a menace on the clay courts, and stunned the world number 23 in straight sets, though the South American’s effort levels were inevitably called into question.
These two last met at the Miami Open earlier this year with Nishikori dismissing his Spanish counterpart in three closely-fought sets, 7-6(2), 6-7(5), 6-1.
But perhaps more pertinent to Monday’s contest will be their head-to-head on clay, equally balanced at one-all.
They met in the third round of last year’s French Open and, again, little could separate the two, with the Japanese eventually triumphing in five sets.
Verdasco won their encounter in Barcelona in 2012 after Nishikori retired and it will be intriguing to see whether the 33-year-old, who tends to produce his best performances in bursts, can end his opponent’s quest for a maiden Grand Slam title.
Prediction: Nishikori in 5