In cervical cancer, the tumor microenvironment (TME) is critical for disease progression, significantly influenced by tumor-associated macrophages (TAMs). This study introduces sialic acid (SA) fortified transferrin (TF) nanoclusters (NCs) for targeted delivery of doxorubicin (DOX), exploiting TF receptor overexpression and siglec interactions within the TME. By incorporating SA, this design enhances the natural tumor-targeting properties of TF, enabling more effective modulation of both TAM and TME modulation. This approach aims at modulating TAMs, shifting the balance towards a pro-inflammatory state. In vitro analysis using a HeLa cell and macrophage co-culture model demonstrated a significant shift in the M1/M2 ratio, correlating with reduced cancer cell proliferation. Key cytokine levels (IL-6, IL-10, and TNF-α) were quantified, providing insights into the mechanism of action. Importantly, in vivo studies using a HeLa+M2 macrophage xenograft model confirmed the strategy\'s efficacy, with noticeable tumor growth reduction. These findings collectively underscore the potential of TF-SA/DOX NCs in modulating the TME to enhance cervical cancer therapy.