Antimicrobial resistance (AMR) and malaria remain significant public health challenges in the WHO Eastern Mediterranean Region (EMR). In 2021, the region reported 1.7 million sepsis-related deaths, with 373,000 associated with bacterial AMR. High antibiotic consumption, particularly in high-income countries, combined with rising usage in middle-income countries, has accelerated the emergence of drug-resistant infections. Malaria management is further complicated by biological threats, including vector insecticide resistance, PFHRP2/3 gene deletions, and antimalarial drug resistance, alongside insufficient trained personnel and limited molecular surveillance capacity. Effective strategies to address these challenges include strengthening regional and cross-border surveillance networks, designating WHO collaborating centers for molecular monitoring, enforcing national treatment policies, and raising public and healthcare provider awareness about rational antimalarial and antibiotic use. These measures, coupled with sustainable funding and enhanced therapeutic efficacy studies, are essential to reduce the development and spread of drug-resistant malaria and improve overall health outcomes in the EMR.