NF-κB is a key regulator of macrophage function in cancer, influencing tumor-associated macrophages (TAMs) polarization toward M2-like or pro-inflammatory M1-like phenotypes. TAMs are major components of the tumor microenvironment (TME), where they can either promote or suppress tumor progression. NF-κB pathways, including canonical, non-canonical, and atypical, regulate TAM polarization by modulating gene expression related to inflammation, immune response, and tumor growth. Targeting NF-κB in the myeloid compartment could help overcome immunosuppression and enhance anti-tumor immunity. In various cancers, such as hepatocellular carcinoma, breast cancer, colon cancer, glioblastoma, and gynecologic cancers, NF-κB plays a critical role in TAM polarization, tumor progression, and immune evasion. For example, in hepatocellular carcinoma, NF-κB activation promotes M2-like TAMs, which support tumor growth, while in breast cancer, NF-κB regulates TAM polarization and EMT processes. In glioblastoma, NF-κB inhibition can shift TAMs toward M1-like macrophages, enhancing anti-tumor activity. Overall, targeting NF-κB pathways represents a promising strategy for cancer immunotherapy.NF-κB is a key regulator of macrophage function in cancer, influencing tumor-associated macrophages (TAMs) polarization toward M2-like or pro-inflammatory M1-like phenotypes. TAMs are major components of the tumor microenvironment (TME), where they can either promote or suppress tumor progression. NF-κB pathways, including canonical, non-canonical, and atypical, regulate TAM polarization by modulating gene expression related to inflammation, immune response, and tumor growth. Targeting NF-κB in the myeloid compartment could help overcome immunosuppression and enhance anti-tumor immunity. In various cancers, such as hepatocellular carcinoma, breast cancer, colon cancer, glioblastoma, and gynecologic cancers, NF-κB plays a critical role in TAM polarization, tumor progression, and immune evasion. For example, in hepatocellular carcinoma, NF-κB activation promotes M2-like TAMs, which support tumor growth, while in breast cancer, NF-κB regulates TAM polarization and EMT processes. In glioblastoma, NF-κB inhibition can shift TAMs toward M1-like macrophages, enhancing anti-tumor activity. Overall, targeting NF-κB pathways represents a promising strategy for cancer immunotherapy.