PURPOSE: To identify, map, and synthesize the individual-level key associations and modes of exposure for hepatitis C virus (HCV) infection in the Middle East and North Africa (MENA), the most affected region by HCV. METHODS: Source of data was the MENA HCV Epidemiology Synthesis Project database, populated through systematic literature searches. Risk factors determined to be statistically significant after adjustment for confounders were extracted and categorized into key associations or modes of exposure. RESULTS: In total, 329 risk factors were identified from 109 articles in 14 of 24 MENA countries. Among key associations, age was most frequently reported (n = 39; 34.2%), followed by other infections/diseases (n = 20; 17.5%), and incarceration (n = 17; 14.9%). Among modes of exposure, health care-related exposures were most frequently reported (n = 127; 59.5%), followed by injecting drug use exposures (n = 45; 20.9%), community-related exposures (n = 34; 15.8%), and sexual-related exposures (n = 8; 3.7%). Blood transfusion, hemodialysis, surgical and other medical procedures, dental work, and medical injections were identified as key health care-related exposures. CONCLUSIONS: Health care appears to be the primary driver of prevalent (and possibly incident) infections in MENA, followed by injecting drug use. HCV screening should target the identified modes of exposure. Commitment to prevention should be an integral component of HCV response to achieve HCV elimination by 2030, with focus on strengthening infection control in health care facilities, improving injection safety and blood screening, and expanding harm reduction services for people who inject drugs.