Biodiversity is currently under strong pressure due to anthropogenic global change. Different drivers of global change may exert direct and indirect effects on biodiversity, and may furthermore interact with one another, but our respective knowledge is still very limited. We investigated indirect and interactive effects of two important drivers of global change, eutrophication and climate change, in replicated low- and high-altitude populations of an insect herbivore, the butterfly Lycaena tityrus, in a laboratory setting. We found local adaptation in developmental traits, with low-altitude populations being adapted to warmer temperatures and longer seasons. Lycaena tityrus responded negatively to agriculturally relevant levels of fertilization of its host plant, showing reduced body mass and prolonged development time. Negative effects were particularly pronounced at warmer temperatures and in high-altitude populations. Our study adds to the increasing knowledge that different drivers of global change may interact and thereby increase the overall level of threat to biodiversity. We suggest that populations inhabiting naturally nutrient-poor environments might be even more vulnerable to agricultural intensification than others, potentially applicable to many species. These findings may have important implications for protecting numerous vulnerable species in the face of rapid environmental change.