Tumor-infiltrating lymphocytes, particularly CD8+ T cells, show circadian oscillations influenced by the internal clocks of leukocytes and endothelial cells. Timing chimeric antigen receptor T cell therapy and immune checkpoint blockade to these rhythms enhances their efficacy. Time-of-day-dependent T cell patterns in murine models predict melanoma patient survival and response to anti-PD-1 therapy, underscoring the significance of circadian dynamics in cancer treatment.