The ESKAPE pathogens ( spp., spp.) are identified to be multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan drug-resistant (PDR); thereby, imposing severe challenges in the treatment of associated infections. ESKAPE pathogens colonize on various biotic and abiotic surfaces; biofilms formed by these pathogens are a potential source for food contamination. Moreover, biofilms play a pivotal role in the development of antimicrobial-resistant (AMR) strains. Hence, the frequent isolation of antimicrobial-resistant ESKAPE pathogens from food products across the globe imposes a threat to public health. A comprehensive understanding of the adhesion signaling involved in the polymicrobial and single-species biofilm will assist in developing alternative preservation techniques and novel therapeutic strategies to combat ESKAPE pathogens. The review provides a comprehensive overview of the signaling mechanisms that prevail in the ESKAPE pathogens for adhesion to abiotic and biotic surfaces and molecular mechanisms associated with poly-microbial biofilm-assisted AMR in ESKAPE.