Mosquito-borne diseases (MBDs) are a group of illnesses transmitted by mosquitoes and can be caused by bacteria, viruses, or parasites. These diseases represent a significant global burden of infectious diseases, including morbidity and mortality. This systematic review delves into the multifaceted factors contributing to the spread of mosquito-borne diseases (MBDs) in the Middle East and North Africa (MENA) region. Following PRISMA guidelines, a thorough analysis of peer-reviewed articles from May 1990 to Jan 2023 was conducted, highlighting the interplay of population, environmental, disease, and mosquito factors in disease transmission and prevalence. The review incorporated 31 studies that revealed a complex relationship between various risk factors and the presence of MBDs. Significant associations were observed with age, certain occupations, environmental conditions such as rainfall and temperature, sanitation practices, specific pathogen variants, clinical symptoms, and Aedes aegypti mosquitoes. Conversely, gender, socioeconomic status, educational status, and certain sanitation-related factors showed inconsistent association with the spread of MBDs. The review underscores the need for targeted interventions, including vector control, improved sanitation, and educational campaigns to mitigate the spread of MBDs in the MENA region. This review could guide research studies to address data gaps and assist in developing effective surveillance programs in the MENA region. This work emphasizes the need for region-specific public health strategies and further research to understand and curb the burden of these diseases effectively.