In the field of Pharmacy, Nursing Practice and Biomedical Sciences, high hospital readmission rates and poor self-management among heart failure patients residing in rural underserved regions. This empirical investigation systematically examines Nurse-Led Telehealth Remote Monitoring for Medication Adherence in Rural Heart Failure Patients through a multi-stage experimental methodology and rigorous quantitative analytical framework. Utilizing randomized clinical trial comparing twelve months of weekly nurse telehealth video visits with standard outpatient care in 210 patients, data were gathered across multiple operational cycles and validated against established international benchmarks. The statistical and computational results reveal that the nurse telehealth intervention reduced 30-day all-cause hospital readmission by 38% and significantly improved patient-reported quality of life. 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 cardiology nursing directors, telehealth program managers, and rural health system administrators. 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.