In the field of Pharmacy, Nursing Practice and Biomedical Sciences, prolonged crisis conditions and high patient mortality trigger severe psychological distress and workforce attrition in intensive care units. This empirical investigation systematically examines Occupational Burnout, Moral Distress, and Psychological Resilience among Critical Care Nurses during Epidemic Surges through a multi-stage experimental methodology and rigorous quantitative analytical framework. Utilizing cross-sectional multicenter study of 420 ICU nurses using Maslach Burnout Inventory and Connor-Davidson Resilience Scale, data were gathered across multiple operational cycles and validated against established international benchmarks. The statistical and computational results reveal that perceived peer support and hospital psychological counseling resources moderated the relationship between moral distress and emotional exhaustion. Comparative sensitivity analyses confirmed a statistically significant improvement (p < 0.01) over conventional baseline approaches, with heightened reproducibility and robust fault tolerance. These comprehensive findings provide actionable theoretical insights and practical implementation guidelines for nurse executives, hospital human resource departments, and healthcare worker wellness committees. Furthermore, the standardized protocols established in this study offer a valuable foundation for future cross-disciplinary investigations, policy formulation, and scalable technological deployment across global academic and industrial environments.