The 21st century has witnessed several clinical outcomes regarding AMR. One health concept has been foreseen as a standard global public health initiative in ensuring human, animal and environmental health. The present study explores critical Gram-negative ESKAPE pathogens encompassing Acinetobacter baumannii (ACB), Klebsiella pneumoniae (KPX) and Pseudomonas aeruginosa (PAE). A comparative genomic analysis approach was utilized for identifying novel and putative genes coercing global health consequences stressing the significance of the above iatrogenic and nosocomial pathogens. O findings reveal that Pseudomonas aeruginosaPAO1 (PAE) possesses the largest genome, measuring 62,64,404 base pairs, containing 14,342 protein-coding genes and an elevated count of ORFs, surpassing other organisms. Notably, P. aeruginosa PAO1 exhibits a comprehensive metabolic landscape with 355 pathways and 1659 metabolic reactions, encompassing 200 biosynthesis and 132 degradation pathways. Transferases are the predominant enzyme category across all three genomes, followed by oxidoreductases and hydrolases. The pivotal role of beta-lactamase in conferring resistance against antibiotics is also evident in all three microbes. This investigation underscores the PAE genome harbours genes and enzymes associated with heightened virulence in antibiotic resistance. The holistic review combined with comparative genomics underlines the significance of delving into the genomes of these antimicrobial-resistant organisms. In silico methodologies are increasingly stressed in aiding the successful accomplishment of the United Nations Sustainable Development Goal -3: Good Health and Well-being. The prominent findings establish Carbapenem resistance and evolutionary lineages of the MCR-1 gene conferring AMR landscapes for future research.