<p>Antimicrobial stewardship (AMS) programmes are central to tackling antimicrobial resistance. Comparative evidence on how barriers differ between high-income countries (HICs) and low-/middle-income countries (LMICs) in tertiary care hospitals is limited. The review aims to identify and compare multilevel barriers to implementing AMS programmes in tertiary care hospitals in HICs and LMICs. We conducted a systematic scoping review following PRISMA-ScR and Joanna Briggs Institute guidance. PubMed and Web of Science were searched for English-language primary studies from January 2015 to November 2025. Studies were considered eligible if they examined barriers to implementing AMS in adult inpatient services in tertiary care hospitals. Using a framework-based thematic approach, barriers were grouped into eight themes and mapped to individual, team, organizational, and system levels. Out of 2311 records, 57 studies met inclusion criteria (23 = HICs, 34 = LMICs). Knowledge, education, and confidence gaps were the most frequent barrier theme in both groups, reported in about three-quarters of studies. Staffing and resource constraints and organisational/governance barriers were also highly prevalent, particularly in LMIC hospitals. Workflow and documentation problems and data-system limitations were more prominent in HIC studies, whereas structural health system constraints were more prominent in LMICs. Qualitative and mixed-methods studies identified a broader range of barriers than surveys or observational designs. AMS implementation in tertiary hospitals is constrained by overlapping multilevel barriers that are broadly similar across income groups but differ in emphasis. Tailored strategies that jointly strengthen workforce capacity, infrastructure and governance are needed, with particular attention to system-level constraints in LMICs and workflow and data challenges in HICs.</p>