Objectives: This study examined the associations between physical, mental, and oral health factors and chewing discomfort among adult workers aged 19–64 years using data from the 9th Korea National Health and Nutrition Examination Survey (2022–2024). Methods: The study included 7,613 adult workers. General characteristics, physical activity, physical health, oral health, and mental health factors were analyzed as independent variables, with chewing discomfort serving as the dependent variable. Data were analyzed using complex sample cross-tabulation and logistic regression. Results: The prevalence of chewing discomfort was 12.4%. It occurred more frequently among workers aged ≥ 40 years, those employed in production roles, and those with lower educational attainment and income levels. A lack of leisure-time physical activity and insufficient aerobic activity were associated with a higher risk of chewing discomfort. Hypertension, diabetes mellitus, hypercholesterolemia, toothache, previous dental implant experiences, poor subjective oral health status, anxiety, and high stress were also significantly associated with chewing discomfort. Conclusions: Chewing discomfort among adult workers is associated with a range of physical, mental, and oral health factors. Therefore, comprehensive multidimensional strategies that encompass chronic disease management, mental health support, physical activity promotion, and preventive oral health care are essential.