<p>The Middle East is confronting a converging public health crisis as gut microbiome dysbiosis and antimicrobial resistance (AMR) amplify in conflict and fragile settings, driven by war, displacement, and systemic healthcare collapse. This review examines the bidirectional relationship between disrupted gut microbiota and escalating AMR, particularly among vulnerable refugee populations and war-affected communities. Key findings reveal alarming resistance rates in <i>ESKAPE</i> pathogens (e.g., <i>Enterococcus faecium</i>,<i> Staphylococcus aureus</i>,<i> Klebsiella pneumoniae</i>,<i> Acinetobacter baumannii</i>,<i> Pseudomonas aeruginosa</i>,<i> and Enterobacter spp</i>), exacerbated by unregulated antibiotic use, malnutrition, and poor sanitation. Dysbiosis fosters AMR through loss of colonization resistance and horizontal gene transfer, while conflict-related healthcare breakdowns—such as empiric antibiotic overuse and absent diagnostics—accelerate resistance spread. Refugee camps, with overcrowding and contaminated water, emerge as critical AMR hotspots. Urgent interventions are needed, including microbiome restoration therapies (e.g., probiotics and faecal microbiota transplantation (FMT), rapid diagnostic tools, and integrated One Health surveillance. Moreover, the increasing trend of AMR is further amplified by the COVID-19 pandemic, which led to widespread antibiotic use and disrupted healthcare services. Review emphasises the importance of regional policy coordination, targeted humanitarian aid focused on microbiome health, and global advocacy to mitigate this crisis, which poses a threat to both local and international health security. Without action, the intersection of dysbiosis and AMR will deepen health inequities in conflict zones, with far-reaching consequences.</p> Graphical abstract <p></p>