The nuclear factor ID3 enhances the anti-tumor activity of macrophages. This study shows that the Kupffer cell lineage-determining factor ID3 controls the balance between activating and inhibitory receptors in macrophages, enabling them to phagocytose live tumor cells and recruit and activate natural killer and CD8 T lymphoid effector cells to restrict tumor growth. ID3 shifts the macrophage inhibitory/activating receptor balance by buffering the binding of the transcription factors ELK1 and E2A at the SIRPA locus. Loss- and gain-of-function experiments demonstrate that ID3 is sufficient to confer this potent anti-tumor activity to mouse bone-marrow-derived macrophages and human induced pluripotent stem-cell-derived macrophages. Expression of ID3 is necessary and sufficient to endow macrophages with the ability to form an efficient anti-tumor niche, which could be harnessed for cell therapy in cancer. The study also shows that ID3 is required for the anti-tumor activity of Kupffer cells, and that its expression in macrophages can be used to enhance their anti-tumor activity. The results suggest that ID3 is a key regulator of macrophage function in cancer, and that its expression in macrophages could be a promising therapeutic target for cancer treatment.The nuclear factor ID3 enhances the anti-tumor activity of macrophages. This study shows that the Kupffer cell lineage-determining factor ID3 controls the balance between activating and inhibitory receptors in macrophages, enabling them to phagocytose live tumor cells and recruit and activate natural killer and CD8 T lymphoid effector cells to restrict tumor growth. ID3 shifts the macrophage inhibitory/activating receptor balance by buffering the binding of the transcription factors ELK1 and E2A at the SIRPA locus. Loss- and gain-of-function experiments demonstrate that ID3 is sufficient to confer this potent anti-tumor activity to mouse bone-marrow-derived macrophages and human induced pluripotent stem-cell-derived macrophages. Expression of ID3 is necessary and sufficient to endow macrophages with the ability to form an efficient anti-tumor niche, which could be harnessed for cell therapy in cancer. The study also shows that ID3 is required for the anti-tumor activity of Kupffer cells, and that its expression in macrophages can be used to enhance their anti-tumor activity. The results suggest that ID3 is a key regulator of macrophage function in cancer, and that its expression in macrophages could be a promising therapeutic target for cancer treatment.