Starting with UFC on ABC: Holloway vs. Kattar, a limited number of fans were allowed inside the newly built Etihad Arena, marking the first time since UFC 248 on March 7, 2020 that non-essential event personnel were in attendance. The venue has maximum capacity of over 18,000, but the UFC was expecting to have closer to 2,000 fans for each of the Fight Island's events during the week.
For the event to be broadcast live during Prime time hours on the east coast of North America, the main card began at 7:00 am (January 24) local time in Abu Dhabi, with a full preliminary card beginning at approximately 4:00 am Gulf Standard Time.
After defending his lightweight title at UFC 254 in October, Khabib Nurmagomedov immediately announced his retirement, citing his father's death from complications related to COVID-19 in last July as the main reason behind it. Despite his announcement, the title was never officially vacated as UFC President Dana White said several times that he believed Nurmagomedov would still fight again. A meeting between both of them to discuss the champion's future was then expected to happen this week during the organization's stint at Fight Island, eventually taking place on January 15. The following day, White made an appearance live on ABC during the main card of UFC on ABC: Holloway vs. Kattar and revealed the outcome of the meeting: the Russian left the door open to a potential return, depending on how the main and co-main event fighters perform at this event, while also praising Charles Oliveira's performance at UFC 256. Despite White's announcement, Nurmagomedov indicated in another interview that "fighting again is not in my plans".
A bantamweight bout between promotional newcomers Umar Nurmagomedov and Sergey Morozov was initially scheduled to take place at UFC 254, but Nurmagomedov pulled out due to an illness. The pairing was then rescheduled for this event. Finally, the bout was set to take place 3 days prior at UFC on ESPN: Chiesa vs. Magny.
A flyweight bout between Amir Albazi and Zhalgas Zhumagulov was expected to take place at UFC on ESPN: Smith vs. Clark, but Zhumagulov pulled out due to visa issues and the bout was rescheduled for this event.
A featherweight bout between Shane Burgos and Hakeem Dawodu was scheduled for the event. However on January 9, Dawodu was forced to withdraw from the bout citing a shoulder injury. The UFC confirmed three days later that Burgos was also injured and the bout was canceled.
On the day of the weigh-ins, a couple of lightweight bouts suffered major changes due to several issues: Ottman Azaitar and Matt Frevola were scheduled to meet in the preliminary portion of the event. However, it was announced that Azaitar was pulled from the bout and had his contract terminated after it was determined that he had violated COVID-19 health and safety protocols, as he attempted to help others enter the UFC's designated safety zone. The other bout that suffered alterations featured Nasrat Haqparast and Arman Tsarukyan. Haqparast withdrew from the bout due to an undisclosed illness and Tsarukyan weighed in at 157 pounds, one pound over the lightweight non-title fight limit. As a result, the promotion arranged a catchweight bout between Frevola and Tsarukyan to keep both athletes on the card. Subsequently, Tsarukyan forfeited 20% of his purse to Frevola as a result of missing weight.