Human pathogenic fungi have emerged as significant causes of morbidity and mortality in patients with acquired immunodeficiency conditions such as HIV/AIDS and receipt of myeloablative chemotherapy and targeted immunosuppressive therapies for autoimmune disorders, neoplastic diseases, and hematopoietic stem cell and solid organ transplantation. In recent years, emerging multidrug resistant Candida auris is responsible for life-threatening outbreaks in healthcare facilities and raises serious concerns to global public health. A recent explosion in the discovery and characterization of novel monogenic inborn errors of immunity that predispose to mucocutaneous and/or invasive tissue-specific fungal disease and the development of clinically relevant animal models of mucocutaneous and invasive fungal infections have collectively enhanced our understanding of cell type-, tissue-, and fungus-specific recognition, effector pathways, and adaptive immune responses. Our improved molecular understanding of fungal virulence traits shows promise for the development of targeted treatment strategies against fungal pathogens. The goal of this Keystone Symposia meeting will build on the 2024 meeting and bring together scientists who study both fungal virulence and fungal immunology, thus helping to synthesize our current understanding of the cellular and molecular determinants of fungal pathogenesis and mammalian antifungal immunity, which will provide the foundation for informing precision risk stratification, prophylactic, therapeutic and vaccination strategies to combat life-threatening fungal infections in vulnerable patient populations.