Health disparities in access to precision oncology represent one of the most pressing challenges in contemporary cancer care, yet limited evidence exists on how emerging targeted radioisotope therapies (TRT) intersect with equity considerations across global and domestic contexts. This mixed-methods systematic review and meta-analysis examined the cost-effectiveness, infrastructure distribution, and equity dimensions of lutetium-177 (Lu-177) prostate-specific membrane antigen-617 (PSMA-617) for metastatic castration-resistant prostate cancer (mCRPC) and Lu-177 DOTATATE for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Drawing on six data sources—GLOBOCAN 2022, IAEA nuclear medicine databases, SEER cancer registries, CMS Medicare claims (2015–2024), published cost-effectiveness analyses, and the Tufts CEA Registry—this study employed random-effects meta-analysis, disparity ratio quantification, incidence rate ratio estimation, and temporal trend analysis across the 2015–2026 timeframe. Results revealed a pooled incremental cost-effectiveness ratio (ICER) of $167,278/QALY for Lu-177 PSMA-617 (k = 8) and $65,097/QALY for Lu-177 DOTATATE (k = 9), suggesting differential value profiles relative to conventional willingness-to-pay thresholds. Globally, a 1,975-fold disparity in PET/CT scanner density between high-income and low-income countries was identified, with incidence-to-mortality ratios of 7.6 in high-income versus 1.3 in low-income countries for prostate cancer. In the United States, Non-Hispanic Black men experienced 64% higher prostate cancer incidence than Non-Hispanic White men (IRR = 1.64, 95% CI: 1.46–1.84), while Medicare data documented a 411.7% increase in Pluvicto utilization from 2022 to 2024. Nigeria and Sub-Saharan Africa emerged as regions with the highest unmet need. These findings demonstrate that TRT adoption is accelerating within systems of profound structural inequality, underscoring an urgent equity imperative for policymakers, health systems, and global health organizations to ensure that the benefits of precision radiopharmaceutical therapy extend to all populations who need them.