Background: A monkeypox (MPOX) outbreak occurred in May 2022. On June 3, 2022, the WHO Blueprint organized a consultation on MPOX research knowledge gaps and priority research questions because the engagement of healthcare providers (HCPs) in providing accurate information and the public's motivation to adapt protective behavior were crucial. Thus, we conducted this study to explore the knowledge issues, animal patterns, and interactions of health care providers in the context of MPOX and COVID- 19 during the MPOX outbreak in 2022. Methods: We conducted a cross-sectional web-based survey among 816 HCWs working in governmental health facilities from many countries, mainly Syria, Egypt, Saudi Arabia, and Cameroon, in September 2022. Use a validated, self-administered questionnaire. Results: Most participants, 460 (56.37%), were of age between 18 and 34 years old; around 52% of our sample were female; 47.79% were single; and 43.26% were married. About 34.44% were physicians, while only 37.25% worked on the frontlines with 60 patients. The majority of participants (79.53%) received vaccinations against COVID-19, whereas only 37.99% and 5.88% received vaccinations against chickenpox and MPOX, respectively. In the meantime, 55.39% had taken courses or training programs regarding COVID-19. Regarding knowledge-seeking behaviours about COVID-19, 38.73% were through passive attention, while only 28.8% got their information through active search. Most of the participants (56.86%) had a moderate level of knowledge regarding COVID. Only 8.82% had courses or training program regarding monkeypox. Regarding knowledge-seeking behaviour about MPOX, 50.86% were through passive attention, while only 18.01% and 23.04% got their information through active and passive search, respectively. Most of the participants (57.60%) had a poor level of knowledge regarding MPOX. Pearson correlation analysis revealed a highly significant correlation between knowledge scores of COVID-19 and MPOX (coefficient = 0.48, p-value < 0.0001). Conclusion: The studied HCPs had poorer knowledge about the MPOX virus than they did about the COVID-19 virus. Training program and education courses had an impact on their knowledge.