The Spanish left-hander, who returned to the ATP circuit only last month after seven months out with a left knee injury, was playing in the Indian Wells Masters final in California on Sunday.
"We are disappointed to hear the news that Rafael Nadal will not be competing in Miami this year, especially given his strong results since his return to the Tour," Sony Open tournament director Adam Barrett said in a statement.
"He is a tremendous ambassador for the game and has thousands of adoring fans here in South Florida. We wish him well and hope to see him back in Miami next year."
Though Nadal has not yet given a reason for his withdrawal from the second ATP Masters 1000 event of the year, it is most likely he was not keen to play successive events on a hardcourt surface where his knee is more vulnerable.
The 11-times Grand Slam champion and claycourt specialist has made a career-best 16-1 start to this season, having won two ATP titles on the clay of South America last month.
His focus will now be fixed on the French Open, starting in late May, as the ATP circuit switches back to clay after Miami for the lead-up to the year's second Grand Slam.