Health and working environment of bus drivers is compromised in low-middle-income countries like Pakistan which leads to burnout and excessive Road Traffic Crashes. Hence, this study delves into factors affecting their safe operations from health and work environment perspectives and measures their associated stress and Burnout level. In a study of four hundred and ninety-nine (499), 86% city and 14% transit bus drivers are surveyed through a questionnaire. Stress is estimated for city and transit bus drivers, using the Effort/Reward Imbalance Model (ERI) of Siegrist, and burnout is calculated using the Copenhagen Burnout Inventory (CBI). For determination of important determinants, descriptive and regression analyses are conducted. Findings show that stress has emerged as negative factor for physical and psychological health of city and transit bus drivers. Results based on bus drivers’ responses suggest that organisational awareness and emphasis on health and safety level can significantly reduce driver stress and burnout. Practitioner summary: This study explores burnout and work-related stress of bus drivers in Lahore (Pakistan). City and transit bus drivers were interviewed through a questionnaire, containing three sections, using different subjective ratings based upon their past reliability. Results indicate that stress in bus drivers emerged as a physical and psychological health-damaging factor.