The Russian, who lost to Italian Jannik Sinner 3-6, 3-6, 6-4, 6-4, 6-3 in the Australian Open final last month, spent a Grand Slam record 24 hours and 17 minutes on court at Melbourne Park.
Medvedev beat Sinner in the Rotterdam final last year.
"Unfortunately I have to pull out of Rotterdam," the 2021 U.S. Open champion said in a statement on Monday.
"After an incredibly tough and long run in Australia my body (and especially my right foot) is not recovered enough yet to play come and defend my title.
"I love playing in Rotterdam, have a long history with the event, and look forward to coming back in 2025."
World number four Sinner will be the top seed at the hard-court tournament following Medvedev's withdrawal, with Andrey Rublev, Holger Rune and Hubert Hurkacz among the other top-ranked players participating in the ATP 500 event.
The tournament takes place from February 12-18.
