Affecting mostly vulnerable populations, including children in the Middle East, antibiotic resistance (AR) is a current major threat to global public health. Although antibiotics are life-saving, their misuse caused a rapid spread of AR. This review describes trends in AR in Middle Eastern pediatric populations of Arab and non-Arab countries over the past decade. The assessment of AR patterns indicated that Staphylococcus aureus and Escherichia coli are the predominant bacteria in Syria. In Egypt, Klebsiella pneumoniae is frequently isolated, while both K. pneumoniae and E. coli were the most common pathogens in Saudi Arabia. Additionally, in Bahrain, Iraq, and Turkey, E. coli was the leading pathogen. Overall, E. coli is widely distributed across several countries, underscoring its importance in pediatric infections. The most common AR pattern observed of E. coli in various countries was to Ampicillin. This was notably documented in studies from Egypt, Saudi Arabia, Bahrain, Iraq, and Turkey, highlighting the prevalence of such AR type in these regions. The latest Middle East AR insights highlight critical trends and challenges threatening global health. This study aims to inform healthcare policies and practices, ultimately improving patient outcomes and decreasing the growing threat of AR in the Middle East and worldwide.