The tumor immune microenvironment (TIME) can limit the effectiveness and often leads to significant side effects of conventional cancer therapies. Consequently, there is a growing interest in identifying novel targets to enhance the efficacy of targeted cancer therapy. More research indicates that tumor-associated macrophages (TAMs), originating from peripheral blood monocytes generated from bone marrow myeloid progenitor cells, play a crucial role in the tumor microenvironment (TME) and are closely associated with resistance to traditional cancer therapies. Lipid metabolism alterations have been widely recognized as having a significant impact on tumors and their immune microenvironment. Lipids, lipid derivatives, and key substances in their metabolic pathways can influence the carcinogenesis and progression of cancer cells by modulating the phenotype, function, and activity of TAMs. Therefore, this review focuses on the reprogramming of lipid metabolism in cancer cells and their immune microenvironment, in which the TAMs are especially concentrated. Such changes impact TAMs activation and polarization, thereby affecting the tumor cell response to treatment. Furthermore, the article explores the potential of targeting the lipid metabolism of TAMs as a supplementary approach to conventional cancer therapies. It reviews and evaluates current strategies for enhancing efficacy through TAMs' lipid metabolism and proposes new lipid metabolism targets as potential synergistic options for chemo-radiotherapy and immunotherapy. These efforts aim to stimulate further research in this area.