Background and Purpose: Jet fuel exposure among military personnel is commonly reported; however, the relationship between exposure and carcinogenic potential in humans is incompletely characterized. Some minor constituents of jet fuel, including benzene, ethylbenzene, and naphthalene, have been established as known or possible human carcinogens; however, whether jet fuels (as a mixture) have the potential to elicit a similar response is not well understood. Previous scientific reviews have identified sparse data on cancer outcomes associated with jet fuel exposure. To assess the potential health effects of occupational exposure to jet fuels used by the Armed Forces, the U.S. Department of Veterans Affairs (VA) conducted a systematic literature review that incorporated data from epidemiologic, animal toxicological, and mechanistic studies to provide a comprehensive assessment and a descriptive weight-of-evidence evaluation to characterize the potential carcinogenic effects of jet fuel exposure. Methods: VA conducted a fit-for-purpose systematic review, adapting the Environmental Protection Agency’s (EPA) Integrated Risk Information System (IRIS) methodology, to assess cancer risk related to jet fuel exposure. The review focused on human (military, occupational, and environmental) exposures, as well as animal and mechanistic evidence of carcinogenicity. All human and animal studies that were included underwent quality evaluations. Given the limited epidemiologic data and VA’s aim for inclusivity, epidemiologic studies rated uninformative were considered in the synthesis and weight-of-evidence call. Mechanistic studies were further categorized based on evidence related to the key characteristics (KC) of human carcinogens. Results: The literature search conducted through January 2024 yielded 4,191 unique references. Title/abstract screening identified 610 potentially relevant studies, of which 42 references reported on cancer outcomes and met the eligibility criteria following full-text review. These included 10 unique primary epidemiologic studies and 12 animal toxicological studies, with additional support from 19 reviews and one case report. Among the 22 epidemiologic and animal toxicological studies that assessed cancer incidence, one was rated as high confidence, one as medium confidence, 18 as low confidence, and two as uninformative. The epidemiologic studies most commonly reported associations between jet fuel exposure and increased overall cancer incidence (n=5) or renal cancer (n=3), while the animal studies most often reported renal (n=3) or dermal (n=3) cancers. An additional 90 studies met the eligibility criteria for mechanistic data. These studies primarily reported on KCs, such as cell proliferation and death (n=43), immunosuppression (n=28), inflammation (n=27), and genotoxicity (n=17). Findings from the mechanistic evidence suggest that jet fuel exposure is associated with induction of inflammation, immunosuppression, and an increase in oxidative stress. Most studies assessing genotoxicity did not identify a correlation between jet fuel exposure and DNA damage. Conclusions: The adaptation of the IRIS and KC frameworks enabled VA to systematically describe the availability and quality of evidence regarding the association between jet fuel exposure and cancer-related outcomes. Applying EPA’s Guidelines for Carcinogen Risk Assessment, VA evaluated the weight-of-evidence for associations between jet fuel exposure and cancer outcomes and found suggestive evidence of carcinogenic potential. This determination is based on observed increases in renal cancer and overall cancer incidence in humans, evidence of renal and dermal cancers in animals, and mechanistic evidence indicating the potential for jet fuel exposure to induce inflammation, immunosuppression, and oxidative stress.