In this seminar, we present the outcome of a comprehensive genomic analysis of multidrug-resistant ESBL-producing E. coli strains isolated from healthy cats and dogs in the United Arab Emirates. Our research represents the initial in-depth genomic investigation into antimicrobial resistance among companion animals in the UAE and the Gulf Cooperation Council nations. The study revealed intriguing results: (i) comprehensively identify genes responsible for virulence factors, (ii) provide genome-based typing of the isolates, (iii) elucidate the mechanisms behind antimicrobial resistance in these strains, and (iv) particularly focus on characterizing the genetic context and phylogenetic relationships of colistin-resistant isolates carrying the mcr-1.1 gene. This contributes valuable insights to the broader regional context of One Health, emphasizes the often underestimated significance of companion animals in the context of antimicrobial resistance epidemiology in the Middle East.