Background: Occupational burnout is a psychological response to chronic workplace stress and is particularly prevalent among nurses due to the high demands of the healthcare environment. In Saudi Arabia, nursing burnout is a growing concern, warranting targeted investigation. Aim/objective: To assess the prevalence of occupational burnout and examine its association with demographic and work-related factors among nurses at King Abdulaziz Hospital, Eastern Province, Saudi Arabia. Methods: The study included 295 purposively selected nurses. Data were collected using two instruments: a self-administered questionnaire covering demographic and work-related characteristics, and the Oldenburg Burnout Inventory (OLBI). Statistical analysis involved chi-square tests and binary logistic regression to identify predictors of burnout. Results: High overall burnout was reported by 8.1% of participants, with 26.8% experiencing high exhaustion and 23.0% high disengagement. Inadequate staffing was significantly associated with burnout (OR = 6.91, p = .001). Working in inpatient units showed a marginal association (p = .054). No other demographic or work-related factors were significantly associated. Conclusions: While the overall prevalence of high burnout was relatively low, a considerable proportion of nurses reported symptoms of exhaustion and disengagement. Perceived inadequate staffing emerged as the strongest predictor of burnout. Interventions such as optimizing nurse staffing levels and integrating stress management into nursing education are essential to mitigate burnout risk.