While not officially announced by the UFC, the promotion was initially targeting a UFC Middleweight Championship unification bout between then champion Georges St-Pierre (who is also a former two time UFC Welterweight Champion) and interim champion Robert Whittaker (also The Ultimate Fighter: The Smashes welterweight winner), to serve as the event headliner. However, St-Pierre later indicated that he is currently mulling his future in the division and announced that he expected to be out indefinitely after being diagnosed with ulcerative colitis. Subsequently, St-Pierre vacated the championship on December 7 and Whittaker was promoted to undisputed champion. Whittaker was then expected to defend the championship against former Strikeforce and UFC Middleweight Champion Luke Rockhold in the main event. However on January 13, it was announced that Whittaker pulled out of the bout and was replaced by former middleweight interim title challenger (as well as 2000 Olympic silver medalist and former world champion in freestyle wrestling) Yoel Romero, who was scheduled to face former WSOF Middleweight and Light Heavyweight Champion David Branch at UFC on Fox 28. The bout is now expected to take place as an interim title contest.

A lightweight bout between Jeremy Kennedy and Alexander Volkanovski was originally scheduled for UFC Fight Night: Werdum vs. Tybura. However, Kennedy pulled out due to a back injury. The pairing was later rescheduled for this event.