Prostate cancer, a leading cause of male cancer mortality, poses major therapeutic hurdles due to its immunosuppressive tumor microenvironment (TME). Here, we link MYC amplification and PTEN deletion to prostate adenocarcinoma metastasis and identify a specific tumor-associated non-classical monocyte subset (staNC-Mo, CD11b+Ly6cLowCD14HiCD43LowCX3CR1Low) as a critical driver of TME immunosuppression. MYC overexpression combined with Pten loss induces mitochondrial stress, triggering tumor cell apoptosis and HSP60 release. HSP-60-TLR4 signaling activates staNC-Mo to secrete TNF-α, stimulating endothelial G-CSF production and driving staNC-Mo differentiation in bone marrow and spleen. CD14 expressed on staNC-Mo facilitates the phagocytosis of apoptotic tumor cells, subsequently inducing staNC-Mo senescence and promoting TGF-β1 secretion, which in turn upregulates CXCL5 secretion in tumor cells via the PI3K/AKT signaling pathway, thereby reinforcing staNC-Mo chemotaxis. Senescent staNC-Mo additionally secretes IL-18, further suppressing innate and adaptive immunity. Therapeutically, targeting Ly6c, CD14, CXCL5-CXCR2, TLR4, or IL-18 signaling pathways effectively reduces staNC-Mo chemotaxis, alleviates TME immunosuppression, and attenuates tumor progression, highlighting promising strategies to restore immune surveillance in advanced prostate cancer.