Prostate cancer (PCa) can remain asymptomatic for years, complicating early detection and effective intervention. Predictive, Preventive, and Personalized Medicine (3PM) provides a transformative framework for addressing these challenges by integrating novel biomarkers, targeted prevention, and individualized therapies. Recent studies highlight the pivotal role of dysregulated microRNAs (miRNAs) and epigenetic alterations in cancer progression and metastasis. miRNAs, as non-coding RNAs approximately 22 nucleotides in length, regulate gene expression through translational inhibition or mRNA degradation. Dysregulated miRNAs are linked to the overexpression of oncogenic proteins and suppression of tumor suppressor genes in malignancies. Polyphenols such as curcumin, quercetin, resveratrol, and green tea catechins (EGCG) have demonstrated potential in modulating miRNA expression and reversing aberrant epigenetic modifications. Despite their established anticancer effects, the clinical application of polyphenols in stratified patient groups, particularly in primary and secondary cancer prevention, remains underexplored. Beyond their anti-inflammatory and antioxidant properties, polyphenols modulate early epigenetic and biogenetic events critical for cancer prevention and therapy. By targeting predictive biomarkers and improving therapy response, polyphenols contribute significantly to 3PM by enabling early diagnostics, mitigating risks, and personalizing treatments. This review evaluates current knowledge of polyphenols' impact on miRNAs and epigenetics in PCa and explores their potential applications within the 3PM framework, emphasizing predictive diagnostics, targeted prevention, and personalized treatment strategies.