Antimicrobial resistance (AMR) represents one of the most pressing global health challenges, with the Middle East emerging as a region of particular concern due to escalating resistance rates across multiple pathogen classes. This mini review synthesizes current evidence on the epidemiology, contributing factors, and intervention strategies related to antibiotic resistance in Middle Eastern countries. A comprehensive analysis of literature published between 2020 and 2025 reveals alarmingly high prevalence rates of multidrug-resistant organisms, including carbapenem-resistant Enterobacteriaceae (CRE), methicillin-resistant Staphylococcus aureus (MRSA), and extended-spectrum β-lactamase (ESBL)-producing bacteria across the region. Key drivers identified include unrestricted over-the-counter antibiotic availability, inadequate antimicrobial stewardship programs, insufficient infection prevention measures, and limited surveillance infrastructure. The COVID-19 pandemic has further exacerbated resistance patterns through increased empirical antibiotic prescribing. Regional variations exist, with Gulf Cooperation Council countries demonstrating more advanced surveillance capabilities compared to conflict-affected nations. This review highlights the urgent need for coordinated regional action, strengthened antimicrobial stewardship implementation, enhanced laboratory capacity, and policy reforms to address this escalating public health crisis. Evidence-based strategies tailored to regional socioeconomic and healthcare contexts are essential for mitigating the AMR burden in the Middle East.