Aim:This study aims to evaluate the long-term efficacy of targeted drug therapies in managing chronic diseases such as hypertension, diabetes, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD), with a focus on disease activity reduction, safety profiles, and improvements in quality of life and functional status. Materials and Methods:A prospective, observational cohort study was conducted over 5 years, enrolling 130 patients diagnosed with chronic diseases. Patients were divided into two groups: one receiving targeted drug therapies and the other receiving standard care. Clinical assessments, laboratory tests, imaging studies, and patient-reported outcomes were collected at baseline, 6 months, 1 year, and annually thereafter. Primary endpoints included changes in disease activity scores, while secondary endpoints focused on functional status, adverse drug reactions, and hospitalization rates. Statistical analysis involved paired t-tests and chi-square tests. Results:At baseline, the two groups were well-matched in terms of age, gender, and comorbidities. After one year, the targeted drug therapy group showed significantly greater reductions in disease activity scores across all conditions, with improvements in hypertension (p = 0.001), diabetes (p = 0.004), rheumatoid arthritis (p = 0.015), and COPD (p = 0.020). Safety outcomes, including adverse events and hospitalization rates, were similar between both groups. The targeted drug therapy group also reported significantly greater improvements in quality of life (p = 0.003) and functional status (p = 0.014). Conclusion:Targeted drug therapies were more effective than standard care in managing chronic diseases, providing significant reductions in disease activity and improvements in quality of life and functional status. The safety profiles were comparable between the two groups, highlighting the long-term benefits of targeted therapies for chronic disease management.