Tumor-infiltrating myeloid cells are a prominent feature of most solid malignancies. This inflammatory immune response, driven by tumor-intrinsic signaling pathways, is a major checkpoint to therapeutic efficacy achieved with immunotherapy and standard cytotoxic therapies. To overcome therapeutic resistance mediated by cancer inflammation, ongoing clinical trials are evaluating strategies that (1) deplete myeloid cells from tumors, (2) inhibit tumor-promoting properties of myeloid cells, and (3) redirect myeloid cells with tumor-inhibitory activity.