The available dominant water, energy, and food (WEF) technologies are responsible for the expansion of pathogenic exposure via climate change and land change at the global scale: there are 1415 known pathogens and 175 are emerging ones, described in the last 40 years. Expansion of xenobiotic exposure is occurring due to the production of 250,000 compounds and an average of 4400 new ones each year. Avariety of pathogenic and WEF xenobiotic agents affecting the human species is charted here. The basal pathogenic human exposome (or lifelong exposure) and the anthropogenic exposome expansion are related to the human bodily systems, to highlight concurrent damages. Foremost among interactions are cancers, which most often result from several mutations after exposure to pathogens or xenobiotics. Of particular interest are emerging pathogens with different bodily effects, and pathogen–xenobiotic interactions, which affect the reproductive/ endocrine/developmental systems: these systems are under anthropogenic evolutionary pressure. WEF technologies form an intertwined nexus such that phaseout of a few dominant but obsolete technologies can effect crucial changes in current human health trends. Prevention is of essence, which means that already available, sustainable, technologies have to be implemented.