The COVID-19 Omicron variant and its subvariants are now the dominant variants circulating in the US. Therefore, the original COVID-19 vaccine cannot offer full protection. Instead, vaccines that target the spike proteins of the Omicron variants are warranted. Hence, the FDA recommended the development of a bivalent booster. Unfortunately, despite the safety and immunogenicity of the Omicron bivalent boosters from Pfizer and Moderna, uptake in the US has been poor. At this time, only 15.8% of individuals in the US aged five and older have received the Omicron bivalent booster (OBB). The rate is 18% for those aged 18 and older. Poor vaccine confidence and booster uptake are often fueled by misinformation and vaccine fatigue. These result in more problems associated with vaccine hesitancy, which are particular prevalent in Southern states in the US. In Tennessee, the OBB vaccination rate for eligible recipients is only 5.88% at time of writing (16 February 2023). In this review, we discuss (1) the rationale for developing the OBBs; (2) the efficacy and safety of the bivalent boosters; (3) the adverse events associated with these boosters; (4) vaccine hesitancy associated with the OBBs uptake in Tennessee; (5) implications for vulnerable populations, disparities in uptake of OBBs in Tennessee, and strategies to improve vaccine confidence and OBB uptake. In support of public health, it is essential that we continue to provide education, awareness, and vaccine access to the vulnerable and medically underserved populations in Tennessee. Receiving the OBBs is the most effective method to date of protecting the public against severe COVID disease, hospitalization, and death.