We report herein an innovative approach to prostate tumor therapy using tumor specific radioactive gold nanoparticles (198Au) functionalized with Mangiferin (MGF). Production and full characterization of MGF-198AuNPs are described. In vivo therapeutic efficacy of MGF-198AuNPs, through intratumoral delivery, in SCID mice bearing prostate tumor xenografts are described. Singular doses of the nano-radiopharmaceutical (MGF-198AuNPs) resulted in over 85% reduction of tumor volume as compared to untreated control groups. The excellent anti-tumor efficacy of MGF-198AuNPs are attributed to the retention of over 90% of the injected dose within tumors for long periods of time. The retention of MGF-198AuNPs is also rationalized in terms of the higher tumor metabolism of glucose which is present in the xanthanoid functionality of MGF. Limited/no lymphatic drainage of MGF-198AuNPs to various non-target organs is an attractive feature presenting realistic scope for the clinical translation of MGF-198AuNPs in for treating prostate cancers in human patients. The comparative analysis of MGF-198AuNPs with other radioactive gold nanoparticles, functionalized either with epigallocatechin gallate or the Gum Arabic, has revealed significantly superior tumoricidal characteristics of MGF-198AuNPs, thus corroborating the importance of the tumor-avid glucose motif of MGF. Oncological implications of MGF-198AuNPs as a new therapeutic agent for treating prostate and various solid tumors are presented.