Immune checkpoint inhibitors (ICIs) have significantly advanced cancer therapy, yet primary and acquired resistance remains a major barrier to durable clinical benefit. This article highlights emerging immunometabolic mechanisms within the tumor microenvironment that may critically influence antitumor immunity and therapeutic response. In addition to classical metabolic suppressors such as glucose deprivation, lactate accumulation, adenosine signaling, and tryptophan catabolism, the manuscript emphasizes three frontier pathways: microbiota-derived metabolites, ferroptosis, and intercellular mitochondrial transfer. Microbiota-associated metabolites can modulate dendritic cell function, T-cell differentiation, and myeloid polarization, thereby shaping immune activity and ICI responsiveness. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is presented as an important link between lipid metabolism and immune regulation, with potential implications for therapeutic vulnerability. Furthermore, mitochondrial transfer between tumor, stromal, and immune cells may promote metabolic dysfunction, T-cell senescence, and immune evasion, ultimately contributing to poor checkpoint inhibitor outcomes. Collectively, these mechanisms expand the current understanding of tumor immunometabolism and suggest new opportunities for biomarker development, patient stratification, and combination therapies. Future studies integrating spatial metabolomics, single-cell multi-omics, and functional metabolic profiling will be essential to identify actionable targets and overcome immunotherapy resistance.