This systematic review evaluates the effectiveness of medication self-management education programs (MSEP) for older adults by analyzing the core characteristics and reported outcomes of successful interventions. Guided by King’s Goal Attainment Theory, this study identifies which program elements, such as scope, provider, and duration, are associated with positive clinical and psychosocial outcomes, aiming to provide evidence-based recommendations for practice and future research amid rising polypharmacy and inappropriate medication use. Methods: A systematic review searched seven databases (up to September 3, 2024) for randomized controlled trials and quasi-experimental studies of medication self-management education for adults 65+. Inclusion followed PICOTS-SD (Participants, Intervention, Comparison, Outcomes, Time, Setting, and Study Design). Quality was assessed (RoB 2.0, ROBINS-I). Data were narratively synthesized, mapping program characteristics to King’s theory (e.g., interaction, transaction) to analyze goal attainment pathways. Results: The 34 included studies demonstrated that MSEP are broadly effective in improving both clinical and psychosocial outcomes. Specifically, comprehensive, multi-session interventions were frequently associated with significant improvements in psychosocial outcomes such as quality of life and self-efficacy, particularly when delivered by multidisciplinary teams or nurses. In contrast, medication-specific programs (14 studies), often led by pharmacists, proved highly effective in enhancing key clinical outcomes, including medication adherence and the reduction of drug-related problems. Conclusion: MSEP effectively enhance adherence. In accord with King’s Goal Attainment Theory, effectiveness is achieved via a ‘transactional’ process. Programs strong in ‘interaction’ (multi-session, nurse-led) achieve psychosocial ‘goal attainment’, while ‘action’-focused programs (pharmacist-led, specific) achieve clinical ‘goals’. The theory may underscore the need for tailored interventions.