Background: Work plays a significant part in all our lives, perceived organizational supportive and work-life balance isn't only important for nurses' health, but also it can improve nurses' workflow and productivity. Aim: To explore the influence of perceived organizational support, work life balance on staff nurses' workflow at Main Mansoura University Hospital. Subjects and methods: Descriptive correlational design was used. Three tools were used for data collection; perceived organizational support scale, work-life balance survey, and nurses' work-related flow inventory. Results: Highly statistically significant relationship between organizational support, work life balance and workflow, highly statistically significant relationship between all levels of organizational support, work life balance and workflow, in addition to staff nurses perceived low organizational support level and moderate level related work life balance and workflow. Conclusion: Highly statistically significant correlation between perceived organizational support, work life balance and workflow. Recommendations: Hospital should monitor the level of all factors regarding their work place, stress; motivation and other benefits will improve balance between work life which in turn will give satisfaction in their personal life, providing an attractive system of recognition and rewards that increase sense of achievement, and personal growth, future research needed between work life balance and workflow.