Methicillin-resistant Staphylococcus aureus (MRSA) presents a significant challenge in healthcare due to its resistance to multiple antibiotics.Antimicrobial resistance (AMR) poses a significant global health threat, necessitating innovative strategies for combating resistant pathogens. The advent of Clustered Regularly Interspaced Short Palindromic Repeats- CRISPR associated protein 9 (CRISPR-Cas9) and deactivated/dead Cas9 (dCas9) technologies has opened up new avenues for precision genome editing and transcriptional regulation, offering promising strategies for controlling AMR.CRISPR-Cas9 through it’s precise genome editing capabilities, allow for targeted disruption of essential genes in MRSA, potentially reversing antibiotic resistance or inhibiting virulence factors. Moreover, the use of deactivated Cas9 (dCas9) fused with regulatory domains enables targeted transcriptional regulation, offering a promising avenue for controlling gene expression in MRSA. This comprehensive review explores the future prospects of CRISPR-Cas9 and dCas9 in addressing AMR, focusing on their potential applications in MRSA and general pathogens. We discuss the utility of CRISPR-based technologies in targeted gene editing for reversing antimicrobial resistance, the development of novel antimicrobials, precision antibiotic sensitization, surveillance and diagnostics. This review discusses recent advancements, challenges, and future prospects of utilizing CRISPR-Cas9 and dCas9 in combating MRSA infections.