In the field of Pharmacy, Nursing Practice and Biomedical Sciences, rapid emergence of multidrug-resistant MRSA clones threatens hospital infection control and empirical antimicrobial efficacy. This empirical investigation systematically examines Genomic Surveillance and Antimicrobial Resistance Profiles of Methicillin-Resistant Staphylococcus aureus in ICUs through a multi-stage experimental methodology and rigorous quantitative analytical framework. Utilizing whole-genome sequencing (WGS), SCCmec typing, and broth microdilution susceptibility testing of 160 clinical bloodstream isolates, data were gathered across multiple operational cycles and validated against established international benchmarks. The statistical and computational results reveal that the dominant ST239-SCCmec III lineage exhibited high-level mupirocin and ciprofloxacin co-resistance requiring targeted contact precautions. 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 hospital epidemiologists, clinical microbiologists, and antimicrobial stewardship 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.