This review discusses the role of NF-κB in governing tumor-associated macrophages (TAMs) and their impact on cancer progression. TAMs, a major component of the tumor microenvironment (TME), exhibit plasticity and can adopt either M1-like (pro-inflammatory) or M2-like (anti-inflammatory) phenotypes. NF-κB transcription factors play a central role in regulating TAM polarization, often driving them towards an M2-like phenotype, which promotes tumor growth and immunosuppression. Targeting the NF-κB pathway in TAMs is thus an attractive therapeutic strategy to overcome immunosuppression and enhance anti-tumor immunity. The review highlights the complex interactions between TAMs and various stimuli, including chemokines, cytokines, and stress signals, which influence their polarization. It also explores the involvement of specific proteins and pathways, such as sphingosine-1-phosphate (S1P), mechanical stretch (MS), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and TLR4, in TAM polarization. Additionally, the review examines the role of NF-κB in different human cancer types, including hepatocellular carcinoma (HCC), breast cancer, colon cancer, glioblastoma, and gynecologic cancers, providing insights into the mechanisms by which NF-κB influences TAM function and cancer progression. Overall, the review underscores the potential of targeting the NF-κB pathway as a therapeutic approach to combat cancer immunosuppression and enhance anti-tumor immunity.This review discusses the role of NF-κB in governing tumor-associated macrophages (TAMs) and their impact on cancer progression. TAMs, a major component of the tumor microenvironment (TME), exhibit plasticity and can adopt either M1-like (pro-inflammatory) or M2-like (anti-inflammatory) phenotypes. NF-κB transcription factors play a central role in regulating TAM polarization, often driving them towards an M2-like phenotype, which promotes tumor growth and immunosuppression. Targeting the NF-κB pathway in TAMs is thus an attractive therapeutic strategy to overcome immunosuppression and enhance anti-tumor immunity. The review highlights the complex interactions between TAMs and various stimuli, including chemokines, cytokines, and stress signals, which influence their polarization. It also explores the involvement of specific proteins and pathways, such as sphingosine-1-phosphate (S1P), mechanical stretch (MS), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and TLR4, in TAM polarization. Additionally, the review examines the role of NF-κB in different human cancer types, including hepatocellular carcinoma (HCC), breast cancer, colon cancer, glioblastoma, and gynecologic cancers, providing insights into the mechanisms by which NF-κB influences TAM function and cancer progression. Overall, the review underscores the potential of targeting the NF-κB pathway as a therapeutic approach to combat cancer immunosuppression and enhance anti-tumor immunity.