Prostate cancer progression is significantly affected by its tumor microenvironment, in which mesenchymal cells play a crucial role. Stromal cells are modified by cancer mutations, response to androgens, and lineage plasticity, and in turn, engage with epithelial tumor cells via a complex array of signaling pathways and ligand-receptor interactions, ultimately affecting tumor growth, immune interaction, and response to therapy. The metabolic rewiring and interplay in the microenvironment play an additional role in affecting the growth and progression of prostate cancer. Finally, therapeutic strategies and novel clinical trials with agents that target the stromal microenvironment or disrupt the interaction between cellular compartments are described. This review underscores cancer-associated fibroblasts as essential contributors to prostate cancer biology, emphasizing their potential as prognostic indicators and therapeutic targets.