Solid tumors represent a diverse group of abnormal cell masses that develop within the body’s tissues and are intricately linked to their microenvironment, commonly referred to as the tumor microenvironment (TME). The TME encompasses the surrounding cellular and noncellular components that interact with tumor cells, influencing their behavior and growth. Current treatments such as chemotherapy, radiation, and surgery are problematic due to tumor growth, invasion, and components of TME. Understanding the complex relationship between solid tumors and their microenvironment is crucial for developing targeted therapies that take into account the intricate signaling networks and molecular interactions occurring within this specialized niche. A significant portion of the TME of numerous solid tumors consists of an inflammatory infiltrate, with macrophages being the predominant cells in many of them. Tumor-associated macrophages (TAMs) may either originate from the existing pool of tissue-resident macrophages or be recruited from the bloodstream. These macrophages can also have their origins traced back to progenitor cells in the bone marrow. TAMs are capable of releasing cytokines and growth factors that promote tumor proliferation, survival, and metastasis while inhibiting immune cell function. Therefore, TAMs are an attractive therapeutic target in the treatment of different cancers. This chapter provides a comprehensive overview of the latest research on the nature of TAMs and the development of therapeutic strategies targeting TAMs.