Pharmacist-led medication optimization is increasingly used to address polypharmacy, potentially inappropriate prescribing, and medication-related risk in older people with multimorbidity. However, improvement in medication-related indicators does not necessarily translate into fewer hospitalizations, lower mortality, fewer falls, better function, or improved quality of life. To determine when pharmacist-led medication optimization is associated with improved outcomes by distinguishing intervention components, practice settings, patient contexts, and outcome domains. A structured search-and-screening process yielded 58 unique records after DOI/title deduplication. All 58 records were assessed against predefined eligibility criteria; 20 were excluded and 38 sources were included. The included evidence comprised clinical systematic reviews and meta-analyses, primary pharmacist-led medication-optimization studies, and methodological sources required for review conduct. Medication review, deprescribing, targeted medication-burden reduction, pharmacist prescribing authority, and multicomponent optimization were analyzed separately. Outcomes were grouped into medication-related, clinical, functional, treatment-burden, and patient-reported domains. Evidence was more consistent for proximal medication outcomes, including prescribing appropriateness, potentially inappropriate medication, medication burden, and drug-related problems, than for mortality, hospitalization, falls, quality of life, and other distal outcomes. Intervention effects varied across settings and populations, although these cross-study patterns did not establish causal moderation. Pharmacist-led medication optimization should not be treated as a uniform intervention or judged by medication count alone. Interpretation requires alignment among the medication problem, pharmacist role, patient vulnerability, practice setting, follow-up, and outcome selected.
