The COVID-19 pandemic presented many psychological stressors which affected healthcare worker wellbeing. The aim of this study was to understand the factors that affect the wellbeing of healthcare professionals in the Kingdom of Saudi Arabia using Job-Demand and Resource (JD-R) Model. The proposal model consisted of demand factors (Work load—job demand, loneliness—personal demand), support factors (organizational support—job resource, and resilience—personal resource), mediators (burnout and work engagement), and outcome (wellbeing) A cross-sectional, descriptive study was conducted across 276 healthcare workers from hospitals and primary healthcare centers, including healthcare professionals, health associate professionals, personal care workers, health management and support personnel, and health service providers, and others between February-March 2022. The proposed model was tested using partial least squares structural equation modeling. Among the respondents, the majority were female (198, 71,7%), married (180, 65.2%), healthcare professionals (206, 74.6%), being more than 10 years in the profession (149, 51.6%), and non-Saudi nationality (171, 62.0%). Burnout accounted for a significant effect on wellbeing. Of the demands (workload and loneliness) and the resources (organizational support and resilience), workload had the greatest impact on burnout. Healthcare organizations should invest in reducing workloads and promoting resilience to reduce burnout and increase healthcare worker wellbeing.