Despite advances in metastatic colorectal cancer (mCRC) treatment, it remains the second-leading cause of cancer-related deaths, with limited therapeutic options. EGFR inhibition is a first-line treatment for mCRC without KRAS mutations, but resistance persists in some patients. Preclinical murine CRC models have shown that EGFR deletion in myeloid cells results in smaller tumors, while the presence of EGFR-positive myeloid cells correlate with poor survival in mCRC patients. However, the role of these cells in tumor progression remains unclear. In this study, we used preclinical mouse models, scRNA-seq, proteomics, and mCRC patient data to investigate the impact of EGFR expression in myeloid cells on the tumor microenvironment (TME) and explore its therapeutic potential. We demonstrate that EGFR deletion in myeloid cells of tumor-bearing CRC mice reduces tumor growth, while EGFR deletion in tumor cells alone has no therapeutic effect. EGFR disruption also decreases F4/80hi macrophages, particularly Spp1+ and C1qc+ subsets, and reduces inflammatory signaling like TGFβ, IFNγ, JAK/STAT in myeloid cells. This, in turn, affects their interaction with T cells, promoting a shift towards a less immunosuppressive TME. Additionally, we identify reduced immune checkpoint expression and thrombospondin-1 (Thbs1) as a myeloid-derived ligand interacting with T-cells. Validation in human CRC shows that high expression of EGFR and THBS1 correlates with poorer prognosis. These findings highlight EGFR signaling in myeloid cells as a key modulator of the TME and suggest targeting EGFR in specific myeloid subsets could improve CRC treatment strategies.