Background <p>Vaccine hesitancy remains a significant challenge to public health efforts in combating COVID-19. This study aims to estimate the prevalence of vaccine hesitancy, booster dose uptake, and related drivers in young nursing students in Morocco.</p> Methods <p>This study was conducted as a cross-sectional investigation among nursing students at a training institute. Data on demographic characteristics, vaccination history, and perceptions regarding COVID-19 and vaccination were collected using a structured questionnaire. Statistical analyses identified the main determinants of vaccine hesitancy and the prevalence of the booster dose uptake.</p> Results <p>The study found a vaccine hesitancy rate of 43.49% among participants. Despite 90.97% receiving the first dose, booster dose uptake remained alarmingly low at 6,87%. Women exhibited significantly higher hesitancy than men (<i>p</i> = 0.002), with 67.13% of women citing concerns about vaccine safety, compared to 24.6% of men. Additionally, individuals without comorbidities were more hesitant to vaccinate (<i>p</i> = 0.031), potentially reflecting a lower perceived severity of COVID-19. Concern about side effects (OR = 4.930, <i>p</i> = 0.031) and insufficient vaccine information (OR = 2.214, <i>p</i> = 0.035) were significant predictors of hesitancy. Interestingly, a positive association was observed between a history of seasonal flu vaccination and willingness to accept COVID-19 vaccination (OR = 0.464, <i>p</i> = 0.047).</p> Conclusions <p>The study highlights critical barriers to COVID-19 vaccination and booster dose uptake among nursing students from Morocco, emphasizing the need for targeted public health strategies. Addressing safety concerns, enhancing vaccine education, and promoting the benefits of booster doses are crucial to improving vaccination rates, especially in a context where emerging epidemics increasingly require immunization campaigns.</p>