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Howard Goldberg, president of the WBF, has announced that the South African veteran will take on the American at Montecasino in a tournament co-promoted by ShowPony and the Southern Sun Group.
The title became vacant when Evander Holyfield relinquished the belt to challenge Alexander Povetkin for the WBA regular title in December.
The 39-year-old Grant, who has a record of 48-5-3, with 29 knockouts, was stopped by Lennox Lewis in two rounds in April 2000 when challenging for the Briton's heavyweight title.
Botha, 43, a former IBF champion, received the same treatment from Lewis three months later when he was also stopped in two rounds.
The "White Buffalo," who has been in with some of the best heavyweights of his era, has a record of 48-5-3, with one no-contest and 28 wins inside the distance. He recently stopped Flo Simba to resurrect his career.
Four other WBF championship fights will be on the bill.
Ilunga Makuba of the Democratic Republic of Congo will fight Pedro Otis from Brazil for the vacant WBF cruiserweight belt. Ali Funeka, Zolani Marali, Malcolm Klassen, Lubabalo Msutu and Rafael Guzman will also be involved in title fights.
