Polymicrobial infections promote the appearance of a network of interactions that can lead to an increase in their antimicrobial tolerance or to the evasion of the host immune system. Pseudomonas aeruginosa and Burkholderia cenocepacia are two multidrug-resistant opportunistic pathogens that significantly influence host health and alter their antibiotic response when in coinfection. Using Galleria mellonella larvae as a model, we examined infection dynamics, immune responses, and antibiotic efficacy in single and coinfections combining acute and chronic P. aeruginosa strains with B. cenocepacia. Larval survival and bacterial dissemination were monitored, revealing tissue-specific infection patterns through confocal microscopy. Larval immunity, bacterial virulence gene expressions and antibiotic susceptibility were also analyzed to characterize host-pathogen dynamics. Our findings revealed that coinfections increased larval lethality and worsened overall health, with B. cenocepacia suppressing melanization and immune responses. Moreover, acute and chronic P. aeruginosa strains increase their virulence gene expression in coinfections. In terms of treatment, an increase of antibiotic susceptibility was observed in coinfected groups compared to single-infections. This study advances understanding of host-pathogen interactions in polymicrobial infections and highlights the need for improved therapeutic strategies.