The reprogramming of cellular metabolism is a fundamental mechanism whereby immune cells respond to infection. The sensing of microbial ligands by myeloid cells promotes dynamic changes in host cell metabolism to deliver a rapid source of energy to support antimicrobial functions. Although the fine-tuned regulation of cellular metabolism is required for the functional activity of myeloid cells, how these processes are coordinated and crosstalk during fungal infection remains unknown. We aim to elucidate the mechanisms whereby host cell metabolism regulates antifungal immunity during the host-fungus interaction, by resorting to cutting-edge research tools in advanced preclinical models and human patients. In particular, we propose to resolve the molecular and cellular mechanisms whereby immunometabolic alterations regulate antifungal immunity, characterize the fungal strategies to counter it, and identify and decode metabolism-related candidate genes of genetic susceptibility to fungal disease. We expect to provide the ultimate proof-of-principle for a pathogenetic model implicating immunometabolic alterations in susceptibility to fungal infection and provide new insights with profound implications for the clinical management of fungal diseases and, more broadly, infectious diseases.