<p>Aflatoxin contamination is a major constraint in global peanut (<i>Arachis hypogaea</i> L.) production, posing significant public health risks and trade restrictions. The toxin, primarily produced by <i>A. flavus</i> and <i>A. parasiticus</i>, is favored by specific environmental and physiological conditions, especially in drought-affected, tropical production systems. Recent advances in plant science reveal that an integrative strategy combining breeding, genomics, and epigenetics offers promising avenues for enhancing aflatoxin resistance. This review synthesizes current knowledge regarding the biological context pathogen behavior, climate impacts, and host plant interactions alongside modern resistance strategies. Under pathogen stress, <i>A. flavus</i> exploits weakened plant defenses and kernel microenvironments to produce aflatoxins. Climate-induced stress, especially drought and heat during pod filling, exacerbates fungal invasion and toxin accumulation. Traditional breeding has identified partial resistance sources, while genomic studies have pinpointed QTLs and candidate resistance genes. Epigenetic mechanisms, including DNA methylation and histone modifications, are emerging as novel regulatory systems that modulate gene expression in response to aflatoxin exposure. Strategically, marker-assisted selection, genome-wide association studies, CRISPR-based editing, and epigenome-wide profiling now enable more precise and durable resistance breeding. This review concludes that combining these tools under integrated frameworks holds the key to developing aflatoxin-resilient peanut cultivars adapted to increasingly variable climates and pathogen pressures.</p>