The emergence of multidrug-resistant (MDR) "superbugs" is a serious threat to world health because of the interdependence of environmental ecosystems, agriculture, and human medicine within the single health framework. Horizontal gene transfer (HGT), residue persistence, and excessive antibiotic use have accelerated the development of antimicrobial resistance (AMR) by 2050, it is predicted that AMR would be responsible for 8.22 million deaths. To evade conventional therapies, bacteria employ sophisticated resistance mechanisms such enzymatic inactivation (e.g., β-lactamases, carbapenemases), target alteration (e.g., PBP2a in MRSA), efflux pumps, biofilm formation, and reduced membrane permeability. In light of this dilemma, new strategies are needed to restore the efficacy of antibiotics and stop the spread of resistance. Advances in antibiotic adjuvants, like efflux pump blockers and β-lactamase inhibitors like avibactam, complement existing drugs to combat resistance. The arsenal against MDR pathogens is further diversified by phage therapy, CRISPR-Cas systems, anti-virulence inhibitors, combinatorial therapy and vaccinations. However, challenges persist, biofilm resilience, plasmid-borne anti-CRISPR defences, and ecological risks of gene-editing tools necessitate rigorous mitigation AI-driven diagnostics, metagenomics, and genomics together offer a revolutionary approach to AMR management and surveillance. To address the superbug epidemic & pandemic, the paper integrates the genetic, molecular, and ecological facets of AMR and highlights the vital need for international collaboration, sustainable practices, and One Health-aligned policies.