INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) threatens global health due to its resistance to vancomycin, which is the standard treatment despite limitations, including nephrotoxicity and low intracellular permeability. This necessitates the development of innovative strategies such as nanocarrier-mediated delivery to overcome such limitations. Nanocarriers serve as delivery systems for vancomycin and exhibit inherent antibacterial properties, potentially providing synergism and overcoming MRSA's resistance. Nanocarriers provide sustained release and targeted delivery of vancomycin to the infection site, achieving higher therapeutic concentrations and superior antibacterial activity with reduced doses, which minimizes systemic toxicity. Moreover, leveraging simulations techniques provides more insights on vancomycin-nanocarrier interactions, facilitating the optimization of nanosystems. AREAS COVERED: The article discusses the potential of nanocarriers in delivering vancomycin to infection site, reducing systemic toxicity, and potentiating anti-MRSA activity. Additionally, it reviews modeling and simulation studies to provide a deeper understanding of vancomycin-nanocarrier interactions. The literature search included experimental articles from 2017 to 2024, searched in Web of Science, Google scholar, PubMed, and Scopus. EXPERT OPINION: Nanocarrier-mediated delivery of vancomycin offers promising approaches to combat MRSA infections by enhancing therapeutic efficacy and reducing systemic toxicity. However, further research is required to optimize these nanoformulations and advance them to clinical trials and practical applications.