Hospital pharmacies are integral to the healthcare system, and evaluating the factors influencing their efficiency and service standards is imperative. This analysis offers global insights to assist in developing strategies for future enhancements. The objective is to identify the optimal Lean Six Sigmamethodologies to improve workflow and quality of hospital pharmacy services. A strategic search, aligned with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, encompassed an extensive range of academic databases, including Scopus, PubMed/Medline, Web of Science, and other sources for relevant studies published from 2009 to 2023. The focus was on management tactics and those examining outcomes, prioritizing publications reflecting pharmacy operations management's state. The quality of the selected articles was assessed, and the results were combined and analyzed. The search yielded 1,447 studies, of which 73 met the inclusion criteria. The systematic review found a low to moderate overall risk of bias. The number of publications roseduring the coronavirus disease (COVID-19) outbreak. Among studies, research output in the United States of Americarepresented26% of the total. Other countries such asIndonesia, Spain, Canada, China, Saudi Arabia, the United Arab Emirates, and the United Kingdom also made significant contributions. Each country accounted for 12%, 8%, 7%, 5%, 5%, 5%, and 5%, respectively. The pharmacy journals led with26 publications, and healthcare/medical with 14. The quality category came next with 12 articles, whileseven journals represented engineering.Studies used empirical and observational methods, focusing on practice quality enhancement. The process control plan had 26 instances, and the define, measure, analyze, improve, and control (DMAIC) was identified 13 times. The sort, set in order, shine, standardize, and sustain (5S)ranked third, totaling seven occurrences. Failure mode and effects analysis (FMEA) and root cause analysiswere moderately utilized, with six and four instances, respectively. Poka-Yoke (mistake-proofing measures) and value stream mappingwere each counted three times.Quality improvement and workflow optimization dominated managerial strategies in 22 (30.14%) studies each, followed by technology integration in 15 (20.55%). Cost, patient care, and staffing each featured in three (4.11%) studies, while two (2.74%) focused on inventory management. One (1.37%) study each highlighted continuing education, collaboration, and policy changes. Analysis of the 73 studies on Lean and Six Sigma in hospital pharmacy operations showed significant impacts, with 26% of studies reporting decreased medication turnaround time, 15% showing process efficiency improvements, and 11% each for enhanced inventory management and bottleneck/failure mode reduction. Additionally, 9% of studies observed decreased medication errors, 8% noted increased satisfaction and cost savings, 6% identified enhancements in clinical activities, 3% improved prescription accuracy, 2% reduced workflow interruptions, and 1% reported increased knowledge.Also, this study has identified key strategies for service delivery improvement and the importance of quality practices and lean leadership. To the best of the author's knowledge, this research is believed to be the first in-depth analysis of Lean and Six Sigma in the hospital pharmacy domain, spanning 15 years from 2009 to 2023.