Objectives This study aimed to assess factors associated with COVID-19 booster dose uptake in the Jazan region, Saudi Arabia. Methods A sample of 467 individuals participated in a cross-sectional online questionnaire between February and March 2022. Data were investigated using descriptive characteristics, Pearson's chi-square, and logistic regression tests. Results Nearly 69.6% of respondents believed the booster dose to be necessary, while 16.3% disagreed, and 14.1% were unsure. Almost two-thirds (61.7%) of the respondents had received the booster dose, while 7.9% had booked a vaccination appointment; the remaining 30.4% had neither received nor scheduled any appointments. Furthermore, 57% of non-vaccinated respondents (n=102) planned to receive the booster dose, 19.0% did not plan to receive the vaccine (n=34), and the remaining 24.0% were hesitant (n=43). Receipt of the booster dose of the vaccine was associated with the respondents' attitude, gender, and having not been previously diagnosed with COVID-19 ( P < 0.05). Men were significantly more than twice as likely to receive the booster dose compared to females, while individuals who had positive attitudes toward the booster dose were up to 5 times more likely to be vaccinated. Conclusions The COVID-19 virus and similar viruses continue to be a possible health risk due to the potential emergence of new, severe variants in the future. Understanding vaccine hesitancy can help manage the acceptance of booster doses and guide the development of targeted awareness campaigns for future disease outbreaks.