Since Saudi Arabia has already confirmed multiple monkeypox (Mpox) cases, it is essential to initiate timely preventive measures, including the implementation of vaccines. In this cross-sectional study, an online survey was conducted among healthcare workers (HCWs) in Saudi Arabia to understand their willingness to receive the Mpox vaccine. A structured questionnaire was used to gather the data. The study comprised 734 samples. Our study found that among study participants, 52.7% were willing to receive the Mpox vaccine and showed that sociodemographic factors were not significantly associated with vaccine willingness. Previous vaccination history (such as influenza and COVID-19) was significantly associated with Mpox vaccine willingness. The respondents reported that the main reasons for receiving the Mpox vaccine were their trust in the Saudi Health Ministry (57.7%) and their understanding that the vaccine was a social responsibility (44.6%). Furthermore, the majority of the respondents (74.7%) reported that they were motivated by the need to protect themselves, their family and their friends. Insufficient vaccine information and fear of unknown adverse reactions were the most reported reasons for an unwillingness to receive the Mpox vaccine. In conclusion, increasing Mpox vaccine-related awareness and focusing on greater information dissemination to reduce fear and increase vaccine uptake is highly recommended.