Abstract: Tumor associated macrophages (TAMs) are pivotal in shaping the immunosuppressive tumor microenvironment and driving the malignant progression of esophageal squamous cell carcinoma (ESCC). This article provides a systematic review of the mechanisms by which TAMs contribute to ESCC pathogenesis, with a focus on their roles in promoting tumor cell proliferation, angiogenesis, metastasis, and inducing therapy resistance. The evolution of TAMs-targeted strategies, from early depletion and repolarization to emerging approaches such as functional remodeling, phagocytosis checkpoint intervention, and precursor cell targeting, is comprehensively discussed. However, the compensatory and plastic nature of the tumor microenvironment often limits the efficacy of monotherapies. Consequently, combining TAMs-directed therapies with existing modalities—including immune checkpoint inhibitors, chemotherapy, and anti-angiogenic agents—has emerged as a crucial strategy to reverse immunosuppression and overcome clinical resistance. Future research should leverage cutting-edge technologies to decipher TAMs heterogeneity and advance the clinical translation of intelligent drug delivery systems and predictive biomarkers. This review aims to furnish a foundational resource for optimizing the therapeutic landscape of ESCC.