Many studies have shown that urban workers may have a higher acceptance rate of coronavirus disease (COVID-19) vaccine uptake compared to their rural counterparts. As Omicron spreads globally, the COVID-19 booster vaccination has been acknowledged as the primary strategy against this variant. In this study, we identify factors related to the willingness of workers in megacities to take the vaccine booster shots and their main reasons accounting for their booster willingness. This research survey was conducted in megacity H in eastern China, and a total of 1227 employees from different industries were interviewed. The study at hand examines the relationship between various characteristics (including both economic and non-economic factors) of urban employees and their intention/desire to accept the COVID-19 booster shoots. The survey results show that some characteristics, namely work organization, vaccine knowledge, and social network, affect their intention to take COVID-19 vaccine booster shots. Urban employees with a strong work organization, a high degree of vaccine knowledge, and a dense social capital are more likely to receive booster injections than other employees. Therefore, work organization, vaccine knowledge, and social networks provide fundamental entry points for designing enhanced injection strategies to increase the acceptance of COVID-19 vaccines among employees in megacities.