Aim The emergence of venom is an evolutionary innovation that favoured the diversification and survival of snakes. The composition of snake venoms is known in detail from venom gland proteomic data. However, there is still a gap of knowledge about the forces that lead to the expression of different toxins in different proportions in the venom cocktail across space and time. Location World. Time period Modern. Major taxa studied Elapidae and Viperidae. Methods We integrated proteomic data with phylogenetic comparative methods to understand how ecological and biogeographic processes drive the evolution of snake venom. Results We observed that more productive environments favour a more complex venom, with more toxins in similar proportions. We found that taxa that live on islands, where there is lower variability of resources, tended to present less complex venom dominated by few toxins. In such cases, the extent of an island's isolation seems to be a relevant factor for faster fixation of specific venom compositions. Main conclusion We show that ecological and biogeographic processes, which can act differentially over time and space, affect the gene expression of toxins in snake venoms.