Abstract: Anti-programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) as immune checkpoint inhibitors (ICIs) therapy has shown the potential of CD8⁺T cells in treating and possibly curing malignancies. However, only approximately 20% of patients benefit from ICI therapy. Therefore, it is necessary to elucidate the antitumor function of CD8⁺T cells in the immune microenvironment and its molecular and spatial mechanism of action. Stem-like CD8⁺T-cell subsets with the ability of self-renewal, proliferation, differentiation, and killing of tumor cells play a vital role in mediating anti-tumor effects. In this review, we analyzed the roles and evolutionary effects of stem-like CD8⁺T cells in anti-tumor effects.