Background and Objectives: Quality of life (QoL) among healthcare professionals (HCPs) is a critical determinant of workforce performance and patient care. Therefore, the present study aimed to assess QoL and its determinants among HCPs in the Hail region, Saudi Arabia. Methods: In this cross-sectional study, data were collected from 388 HCPs from multiple healthcare facilities using the WHOQOL-BREF questionnaire. The survey was conducted from August 2025 to October 2025. Convenience sampling was used, and QoL domain scores were calculated according to WHO guidelines. We applied Spearman’s correlation test to assess correlations across domains and logistic regression to identify factors associated with individual and overall QoL. Results: Among the HCPs studied, overall QoL had a median score of 80, while the physical, psychological, social, and environmental domains showed moderate scores with considerable variability. We found a significant positive correlation between the various QoL domains (p = 0.001). Non-Saudi nationals (p = 0.010) and participants with chronic diseases (p = 0.032) reported significantly lower overall QoL. Furthermore, age group, work experience, HCPs category, work setting, nationality, and the presence of chronic disease were significant predictors across multiple QoL domains. Conclusions: The findings highlight the need for targeted workplace and health support interventions to manage the mental and physical health of HCPs, particularly for non-Saudi HCPs and those with chronic conditions, through tailored training, education, and lifestyle-based support program