The 135-pound contest will take place on a UFC Fight Night event on May 8. The UFC has not yet announced an official location for the event.
Holm (14-5) is coming off back-to-back unanimous decision wins, against Raquel Pennington in January 2020 and Irene Aldana in October. Her last loss came in a bantamweight title fight against dual-weight champion Amanda Nunes at UFC 239 in July 2019. Holm's past three losses have come with a championship on the line, going back to 2017.
Fighting out of Albuquerque, New Mexico, Holm, 39, will make her fourth straight appearance at 135 pounds, but she has also competed at 145 pounds.
Pena (10-4) is coming off a submission win against former title challenger Sara McMann at UFC 257 last month in Abu Dhabi. Fighting out of Chicago, Pena is 2-1 in her past three appearances, with the loss coming against another former title challenger and featherweight champion in Germaine de Randamie. A win against Holm would catapult her into title contention at 135.