Antimicrobial resistance (AMR) is a growing global health threat, requiring innovative strategies to combat it. This review explores next-generation approaches integrating genomics, CRISPR technology, and novel therapeutics to effectively address AMR. Genomic techniques enable the identification of resistance genes, track their spread, and predict resistance patterns. CRISPR-Cas systems offer precise genome editing to disrupt resistance genes and restore antibiotic sensitivity. Novel therapeutics, such as antimicrobial peptides, bacteriophages, and synthetic biology-derived compounds, provide alternative treatment options. These approaches can bypass traditional resistance mechanisms and exhibit efficacy against multi-drug resistant organisms. Integrating artificial intelligence and machine learning with genomics and CRISPR can accelerate the discovery of new antibiotics and predict resistance trends. Implementing these strategies requires global collaboration, regulatory frameworks, and investment in research and development. By combining genomics, CRISPR, and novel therapeutics, we can create a multifaceted approach to overcome AMR, ensuring effective treatments and safeguarding public health. This integration represents a paradigm shift in antimicrobial strategy, offering hope for a future where resistant infections can be effectively managed and treated. Keywords: Integrating Genomics, Antimicrobial Resistance, CRISPR, Therapeutic.Antimicrobial resistance (AMR) is a growing global health threat, requiring innovative strategies to combat it. This review explores next-generation approaches integrating genomics, CRISPR technology, and novel therapeutics to effectively address AMR. Genomic techniques enable the identification of resistance genes, track their spread, and predict resistance patterns. CRISPR-Cas systems offer precise genome editing to disrupt resistance genes and restore antibiotic sensitivity. Novel therapeutics, such as antimicrobial peptides, bacteriophages, and synthetic biology-derived compounds, provide alternative treatment options. These approaches can bypass traditional resistance mechanisms and exhibit efficacy against multi-drug resistant organisms. Integrating artificial intelligence and machine learning with genomics and CRISPR can accelerate the discovery of new antibiotics and predict resistance trends. Implementing these strategies requires global collaboration, regulatory frameworks, and investment in research and development. By combining genomics, CRISPR, and novel therapeutics, we can create a multifaceted approach to overcome AMR, ensuring effective treatments and safeguarding public health. This integration represents a paradigm shift in antimicrobial strategy, offering hope for a future where resistant infections can be effectively managed and treated. Keywords: Integrating Genomics, Antimicrobial Resistance, CRISPR, Therapeutic.