The study aims to investigate the impact of effort-reward imbalance and fatigue on the self-efficacy of nurses working in tertiary care hospitals. A purposive sampling strategy was used to recruit participants from both the public and private sector hospitals. The sample consisted of (N=91) participants with a mean age of 27 years. Effort Reward Imbalance (ERI-16 item condensed version) scale, along with the Visual Analog Fatigue Scale and General Self-Efficacy tool was used to measure the relationship among these variables. Results showed that there was a significant relationship between fatigue and self-efficacy of nurses. However, age, effort-reward imbalance, and fatigue were the significant predictors of self-efficacy. Married nurses reflected satisfactory levels of self-efficacy as compared to unmarried nurses. Considering the limited resources for data collection, it is advised to consider a collaboration between hospitals and the research committee. Further, there is a need to conduct a longitudinal study followed by interviews to explore personnel reflection among participants.