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Background: Hospital readmissions represent a critical challenge to global healthcare systems, particularly among high-risk patient populations. Nurse-led interventions, including transitional care, discharge education, and telemonitoring, have gained attention as strategies to reduce preventable readmissions. Objective: To systematically review and synthesize peer-reviewed evidence on the effectiveness of nurse-led interventions in reducing hospital readmission rates, and to evaluate associated outcomes including patient satisfaction, costeffectiveness, and quality of life. Methods: A systematic review adhering to PRISMA 2020 guidelines was conducted. Databases searched included PubMed, CINAHL, Scopus, Web of Science, Embase, and Google Scholar. Studies published between 2000 and 2025 that evaluated adult populations receiving nurse-led post-discharge care were included. Outcomes of interest included readmission rates (30-90 days), mortality, cost, and patient satisfaction. Results: Fifteen studies met inclusion criteria, including randomized controlled trials, quasi-experimental designs, and observational studies. Most interventions demonstrated statistically significant reductions in 30-day readmission rates, ranging from 5% to 20%. Transitional care models and structured education were among the most effective approaches. Technology-assisted interventions, such as telemonitoring, showed promise for scalability and impact. Conclusion: Nurse-led interventions are effective in reducing hospital readmission rates, particularly when delivered through structured, patient-centered models. These programs also improve satisfaction, quality of life, and healthcare costefficiency. Broader implementation requires institutional support and contextual adaptability.