Background: The new resurgence of human Monkeypox (Mpox) cases, both within and outside of the central and western African countries, is causing concern among public health officials worldwide. Pediatric physicians play an important role in Mpox surveillance and case management; thus, this study aims to determine the level of Mpox knowledge among pediatric residents in Saudi Arabia. Methods: A cross-sectional study was done from November 21 to December 28, 2022, in Riyadh, the capital of Saudi Arabia involving 128 pediatric residents' physicians chosen through systematic random sampling. A validated, semi-structured, self-administered questionnaire was used to collect data. R-software was used to analyze the data. The chi-square test was used to investigate the relationship between the knowledge score and the sociodemographic independent variables. Results: Among the 128 pediatric residents' physicians who participated in this study, the majority (65.7%) were aged >26 years. More of the respondents were female (57%), married (63.2%), and in their junior level of residency years (48.4%). The majority (66%) of the respondents have good knowledge of Mpox. Being a senior resident, getting a full dose of COVID-19 vaccines, and having recently heard about Mpox outbreaks were statistically significant factors associated with good scores in knowledge about Mpox. The main sources of information were medical education, radio, television, and newspaper. Conclusions: Despite the adequate level of knowledge about the Mpox gap among pediatric residents' physicians, it is recommended that targeted intervention could be a channel through organized continuous medical education and social media to improve the knowledge about any new emergent diseases.