Background: Antimicrobial resistance is driven by excessive and suboptimal antibiotic use in hospitals. Pharmacist-led antimicrobial stewardship (AMS) that explicitly uses microbiology and laboratory biomarkers to guide therapy may optimize antibiotic exposure and improve outcomes, particularly in resource-limited settings and high-risk units. To synthesize evidence on pharmacist-led, laboratory-guided AMS interventions in adult inpatients and describe their clinical and microbiological impact. Methods: A systematic review was conducted according to PRISMA 2020. Electronic databases were searched for interventional or quasi-experimental hospital studies in adults where clinical pharmacists led AMS activities and used laboratory data (cultures, susceptibility testing, procalcitonin, therapeutic drug monitoring, antibiograms) to guide decisions. Two reviewers screened, extracted data, and assessed risk of bias. Results: Five studies met the eligibility criteria, including four quasi-experimental before–after cohorts and one retrospective cohort across neurosurgical intensive care, multidisciplinary medical wards, and tertiary hospitals in Ethiopia, Japan, China, the United States, and the United Arab Emirates. Pharmacist-led, lab guided AMS consistently reduced broad-spectrum antibiotic use, shortened or optimized length of therapy, decreased healthcare-associated Clostridioides difficile infection, lowered multidrug-resistant organism rates, and reduced drug expenditure, with no signal for increased mortality. Prescriber acceptance of pharmacist recommendations ranged from high to very high. Conclusion: Pharmacist-led, laboratory guided AMS programs in adult inpatients are feasible across diverse settings and are associated with improved antimicrobial utilization, better microbiological profiles, and stable or improved clinical outcomes. Wider adoption and high-quality comparative trials are warranted.