Tumor-associated macrophages (TAM) are a major component of the tumor stroma and play a critical role in tumor progression and invasion. They exhibit protumoral functions, such as promoting angiogenesis, matrix remodeling, and suppressing adaptive immunity. Clinical studies have shown that high macrophage content in tumors correlates with poor patient prognosis, and long-term use of non-steroidal anti-inflammatory drugs reduces cancer risk. TAM represent a unique, M2-skewed myeloid population that could be a target for anti-cancer therapy. Chronic inflammation is linked to various cancers, and non-steroidal anti-inflammatory drugs provide protection against tumors. Inflammatory components are present in the microenvironment of most neoplastic tissues. TAM, first identified in the late 1970s, promote tumor growth and are associated with poor prognosis in many human tumors. Recent genomic studies have linked genes related to leukocyte or macrophage infiltration to poor prognosis in lymphomas and breast cancer. Gene-modified mice have helped dissect molecular pathways of inflammation leading to tumor promotion and the role of inflammatory processes in tumor progression. Key factors include TNF, IL-1, CSF-1, CCL2, COX-2, NF-κB, and enzymes involved in tissue remodeling, all essential for carcinogenesis and metastasis. TAM promote tumor progression by facilitating angiogenesis, lymphangiogenesis, ECM remodeling, and adaptive immunity suppression. They can also kill tumor cells, maintaining a "macrophage balance." Inflammatory cytokines like IL-1 and TNF promote metastasis. The functional program of TAM is regulated by NF-κB and HIF-1. These transcription factors are master regulators of TAM transcriptional programs and play central roles in tumor progression and metastasis. Chronic inflammation can induce highly polarized type I or II inflammation, with M1 macrophages promoting anti-tumor responses and M2 macrophages promoting tumor growth. TAM have a phenotype and function similar to type II macrophages, and their activation is influenced by microenvironmental signals. Understanding TAM's role in tumor progression is crucial for developing targeted therapies.Tumor-associated macrophages (TAM) are a major component of the tumor stroma and play a critical role in tumor progression and invasion. They exhibit protumoral functions, such as promoting angiogenesis, matrix remodeling, and suppressing adaptive immunity. Clinical studies have shown that high macrophage content in tumors correlates with poor patient prognosis, and long-term use of non-steroidal anti-inflammatory drugs reduces cancer risk. TAM represent a unique, M2-skewed myeloid population that could be a target for anti-cancer therapy. Chronic inflammation is linked to various cancers, and non-steroidal anti-inflammatory drugs provide protection against tumors. Inflammatory components are present in the microenvironment of most neoplastic tissues. TAM, first identified in the late 1970s, promote tumor growth and are associated with poor prognosis in many human tumors. Recent genomic studies have linked genes related to leukocyte or macrophage infiltration to poor prognosis in lymphomas and breast cancer. Gene-modified mice have helped dissect molecular pathways of inflammation leading to tumor promotion and the role of inflammatory processes in tumor progression. Key factors include TNF, IL-1, CSF-1, CCL2, COX-2, NF-κB, and enzymes involved in tissue remodeling, all essential for carcinogenesis and metastasis. TAM promote tumor progression by facilitating angiogenesis, lymphangiogenesis, ECM remodeling, and adaptive immunity suppression. They can also kill tumor cells, maintaining a "macrophage balance." Inflammatory cytokines like IL-1 and TNF promote metastasis. The functional program of TAM is regulated by NF-κB and HIF-1. These transcription factors are master regulators of TAM transcriptional programs and play central roles in tumor progression and metastasis. Chronic inflammation can induce highly polarized type I or II inflammation, with M1 macrophages promoting anti-tumor responses and M2 macrophages promoting tumor growth. TAM have a phenotype and function similar to type II macrophages, and their activation is influenced by microenvironmental signals. Understanding TAM's role in tumor progression is crucial for developing targeted therapies.