Castration-resistant prostate cancer (CRPC) remains a major clinical challenge after androgen deprivation therapy (ADT), largely due to the establishment of an immunosuppressive tumor microenvironment (TME). Here, through integrated transcriptomic and functional analyses, we identified a previously unrecognized feedforward inflammatory loop involving prostate cancer (PCa) cells, tumor vascular endothelial cells (TVECs), and tumor-associated macrophages (TAMs) that drives CRPC progression. ADT-induced IL-1β expression in PCa cells acted in a paracrine manner on TVECs, stimulating IL-8 and CXCL1 secretion. These chemokines recruited Ly6C^hiCcr2⁺ monocytes, which differentiated into M2-like TAMs and upregulated pentraxin 3 (PTX3). PTX3 directly promoted IL-8 production in PCa cells, reinforcing a self-sustaining inflammatory loop that accelerated CRPC progression. Analysis of clinical specimens confirmed the presence of this IL-1β–PTX3–IL-8 axis in human PCa. Therapeutically, PTX3 blockade with a neutralizing antibody disrupted this loop, suppressed CRPC development, and enhanced the efficacy of docetaxel chemotherapy. Together, these findings reveal a critical immuno-inflammatory crosstalk in the TME that fuels CRPC progression and highlight this feedforward loop as a promising therapeutic target for this lethal disease.