Investigation of venoms sourced from pan-Indian populations of the spectacled cobra (Naja naja) and Russell’s viper (Daboia russelii) from six biogeographical zones has unveiled astounding differences in the venoms of these India’s medically most important snake species. Stark differences in venom composition and potency were observed not only between snake populations separated by large distances (>6000 km) but also within various individuals of the same population at a very fine geographical scale (<50 km). Furthermore, a significant influence of ontogeny and diet on venom composition and specificity was also observed. Overall, we unravel remarkable differences in venom composition, pharmacological activities and potencies, and the consequent alarming repercussions of this variation on the antivenom therapy. Thus, we highlight the significant influence of ecology and environment on venom variability in Indian snakes and the pressing need to innovate pan-India effective antivenoms to safeguard the lives, limbs and livelihoods of India’s hundreds of thousands of annual snakebite victims.