<p>Regulating intracellular phosphorus may affect multiple biosynthetic processes and modulate cancer cell progression. Here we show that exogenous PEGylated black phosphorus nanosheets (BPP) are metabolized into phosphate in tumor cells, where they boost mitochondrial oxidative phosphorylation. This results in the modulation of several signalling pathways, with the attenuation of prosurvival gene expression and reduction in PD-L1 protein expression in melanoma cells, leading to impaired cancer progression. We also reveal that BPP promote the activation of immune regulation, confirmed by the increased proinflammatory cytokine content in serum, high expression of tumour-infiltrating lymphocyte CD8⁺ T cells and lower expression of CD4⁺ regulatory T cells in tumour and lymph nodes. In the spleen, BPP mediate a significant increase in the concentration of effector memory CD8⁺ T cells, inducing a ‘positive regulation’ of the immune microenvironment. The introduction of a PD-1/PD-L1 inhibitor further enhances the immunopotentiation effect. These findings may define BPP as a dual-function tumour chemotherapeutic and immunopotentiator.</p>