<p>The integration of genomics into the One Health framework presents a transformative opportunity to address antimicrobial resistance (AMR), a critical global health challenge impacting human, animal, and environmental well-being. This review explores the intersection of genomics, AMR, and public health, with a focus on cutting-edge tools such as whole-genome sequencing (WGS), metagenomics, and CRISPR-based diagnostics. These technologies enhance our ability to identify resistance mechanisms, track pathogen transmission, and develop targeted interventions. However, significant barriers, including limited bioinformatics capacity, economic constraints, and fragmented governance, hinder the widespread adoption of these tools, particularly in low- and middle-income countries (LMICs). Emerging advancements, such as big data analytics, machine learning, and personalized antimicrobial therapies, offer new pathways to overcome these challenges. This review underscores the urgency of international collaboration and capacity-building initiatives to ensure equitable access to genomic technologies and strengthen AMR mitigation efforts. By harnessing the potential of genomics, the One Health framework can drive innovative solutions to safeguard global health and combat AMR effectively.</p>