Introduction: Antibiotics are widely administered for various indications, leading to increased antimicrobial resistance (AMR) in acute care hospitals. Since the onset of the COVID-19 pandemic, Antimicrobial Stewardship (AMS) effective strategies should be used to maintain the rational use of antibiotics and decrease the threat of Antimicrobial Resistance (AMR). Aim: To investigate the AMS intervention Pre-pandemic (PP) and During-the-pandemic (DP) from the literature. Design and Setting: Systematic review of primary studies on AMS implementation in acute care settings. Methods: Relevant studies published between 2000 and March 2021 were obtained from Medline (via PubMed), Embase, OVID, CINAHL, International Pharmaceutical Abstracts, Psych Info, Scopus, Web of Science, Cochrane Library, OpenGrey, and Google Scholar, using a comprehensive list of search terms. Public Health England (PHE) toolkit was agreed as a gold standard for the AMS intervention strategies. The methodological quality of included studies was assessed using the Critical Appraisal Skills Programme (CASP) Programme. Results: There were 8763 articles retrieved from the databases. Out of these, 16 full-text articles met the inclusion criteria for the review. The AMS implementation was identified as AMS strategies, which include core and supplemental strategies and AMS measures PP and DP. Conclusion: This Systematic review summarises AMS implementation strategies and measures. Appropriate interventions appeared to be effective in maintaining the proper use of antibiotics and decreasing the AMR threat, especially DP. Further studies to investigate AMS implementation presented in this systematic review are imperative.