Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment, and their invasion in tumors is closely related to poor prognosis. Although TAMs are recognized as therapeutic targets, their heterogeneity makes studying tumor mechanism and developing drugs targeting TAMs difficult. The study of TAMs heterogeneity can be used to analyze the mechanism of tumor progression and drug resistance, and may provide possible treatment strategies for cancer patients. Single-cell RNA sequencing (scRNA-seq) can reveal the RNA expression profile for each TAM to distinguish heterogeneity, thereby providing a more efficient detection method and more accurate information for TAM-related studies. In this review, by summarizing the research progress in macrophage heterogeneity and other aspects of scRNA-seq over the past five years, we introduced the development of scRNA-seq technology and its application status in solid tumors, analyzed the advantages and selections of scRNA-seq in TAMs, and summarized the detailed specific research fields. To explore the mechanism of tumor progression and drug intervention from single cell level will provide new perspective for personalized treatment strategies targeting macrophages.