Aflatoxins (AFs), harmful secondary metabolites produced by the genus , particularly and , are one of the best-known potent mycotoxins, posing a significant risk to public health. The primary type, especially aflatoxin B (AFB), is a potent carcinogen associated with liver cancer, immunosuppression, and other health problems. Environmental factors such as high temperatures, humidity, and inadequate storage conditions promote the formation of aflatoxin in staple foods such as maize, peanuts, and rice. Immunocompromised individuals, including those with HIV/AIDS, hepatitis, cancer, or diabetes, are at increased risk due to their reduced detoxification capacity and weakened immune defenses. Chronic exposure to AF in these populations exacerbates liver damage, infection rates, and disease progression, particularly in developing countries and moderate-income populations where food safety regulations are inadequate and reliance on contaminated staple foods is widespread. Biomarkers such as aflatoxin-albumin complexes, urinary aflatoxin M, and aflatoxin (AF) DNA adducts provide valuable insights but remain underutilized in resource-limited settings. Despite the globally recognized health risk posed by AF, research focused on monitoring human exposure remains limited, particularly among immunocompromised individuals. This dynamic emphasizes the need for targeted studies and interventions to address the particular risks faced by immunocompromised individuals. This review provides an up-to-date overview of AF exposure in immunocompromised populations, including individuals with cancer, hepatitis, diabetes, malnutrition, pregnant women, and the elderly. It also highlights exposure pathways, biomarkers, and biomonitoring strategies, while emphasizing the need for targeted interventions, advanced diagnostics, and policy frameworks to mitigate health risks in these vulnerable groups. Addressing these gaps is crucial to reducing the health burden and developing public health strategies in high-risk regions.