Tumor microenvironment (TME) has become a major focus of cancer research as a promising therapeutic target. TME comprises cancer cells surrounded by nonmalignant cells, vessels, lymphoid organs, immune cells, nerves, intercellular components, molecules and metabolites located within or near the tumor lesion. Neuromedin U (NMU), a secretory peptide identified in the TME, has gained much attention as an important player in cancer and nonmalignant cell crosstalk. NMU receptors were detected in cancer cells as well as in nonmalignant TME components, such as immune, stromal and endothelial cells. We propose here to discuss the concept that NMU secreted by cancer cells activates cellular components of TME and thus contributes to the formation of microenvironment that favors tumor growth and cancer progression. We summarized the available data on cancer tissues and cell types that have been identified as a source of NMU and/or receptor-expressing NMU targets. We made a critical selection of NMU-receptor positive cell types that are known components of the TME of most malignant tumors. Finally, we discussed whether NMUs and NMU receptors represent a potential therapeutic target for cancer treatment, and summarized information on the tools available to modulate their activity.