Abstract Candida albicans is the most common, opportunistic human fungal pathogen whose complex interplay with the host innate immune system remains incompletely understood. In this study, we revealed that infection macrophages with C. albicans triggers prominent cell death, which is largely attributed to the RIPK3/MLKL–mediated necroptosis. Our results further demonstrated that the TSC1-mTOR pathway plays a pivotal role in the control of macrophage necroptosis upon engaging the Dectin-1/2 and TLR-2/4 pathways through fungal components β-glucan/α-mannan or Sel1, respectively. Notably, the rapamycin-sensitive mTORC1 pathway, rather than the rapamycin-insensitive mTORC2 pathway, was responsible for elevated activation of RIPK1, RIPK3, and MLKL in TSC1-deficient macrophages. Following systemic infection with C. albicans, mice with macrophage/neutrophil–specific deletion of Tsc1 (Tsc1M/N−/−) showed heightened fungal burden in multiple organs, such as the kidney, liver, and spleen, severe morbidity, and mortality. Notably, Tsc1M/N−/− kidneys exhibited prominent cell death and concomitant loss of tissue-resident macrophages, which likely contributing to a dampened phagocytosis of fungal pathogens. Together, our data demonstrate a crucial role for the TSC1-mTOR pathway in the regulation of macrophage necroptosis and suggest that both Dectin- and TLRs-induced necroptosis may undermine the immune defense effector functions of these innate receptors during C. albicans infection.