Fumonisins, primarily produced by Fusarium verticillioides, are a group of mycotoxins commonly found in maize and maize-based products, posing a significant global food safety concern due to their carcinogenic and systemic toxic potential. Fumonisin B1 (FB1), the most prevalent and toxic variant, has been classified as a Group 2B carcinogen by the IARC and is strongly associated with esophageal and liver cancers, as well as nephrotoxicity. Mechanistically, FB1 disrupts sphingolipid metabolism by inhibiting ceramide synthase, resulting in apoptotic imbalance, oxidative stress, and epigenetic dysregulation—hallmarks of carcinogenesis. Epidemiological studies in high-risk regions, such as northeastern Iran and southern Africa, support a strong correlation between dietary FB1 exposure and elevated cancer incidence. Moreover, FB1 has been linked to renal carcinogenesis in rodent models, where the kidney’s proximal tubules display heightened sensitivity to sphingolipid perturbation. Given its environmental resilience and food chain persistence, effective control of fumonisins demands an integrated farm-to-fork approach. Strategies include pre- and postharvest interventions, biological controls using Trichoderma and Bacillus species, and emerging chemical detoxification techniques like ozonation and enzymatic hydrolysis. Despite promising advances, challenges remain—particularly in regulatory approval, affordability, and field scalability. This chapter also highlights rapid detection technologies and potential therapeutic responses for fumonisin-induced liver cancer. India’s experience with mycotoxin outbreaks underscores the urgency of strengthening food safety surveillance and public health awareness. Collectively, this work reinforces fumonisin’s significant public health implications and the necessity for multidisciplinary mitigation efforts that span agriculture, toxicology, biotechnology, and public policy.