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The proper functioning of the immune system requires an adequate balance between myeloid and lymphoid populations. Tumor growth alters this balance, also through the dramatic expansion of immunosuppressive myeloid populations, which block specific immunity, fueling tumor growth and dissemination and limiting the effectiveness of antitumor therapies, including immunotherapy. Tumors alter the expansion and functions of myeloid cells by acting locally in the tumor microenvironment, as well as on myeloid progenitors, through the manipulation of metabolic traits that govern their functions. The understanding of these metabolic alterations and their clinical translation is expected to offer new valid therapeutic options.