High‐Z metal‐based nanoscale metal–organic frameworks (nMOFs) with photosensitizing ligands can enhance radiation damage to tumors via a unique radiotherapy‐radiodynamic therapy (RT‐RDT) process. Here we report Monte Carlo (MC) simulation‐guided design of a Th‐based nMOF built from Th6‐oxo secondary building units and 5,15‐di(p‐benzoato)porphyrin (DBP) ligands, Th‐DBP, for enhanced RT‐RDT. MC simulations revealed that the Th‐lattice outperformed the Hf‐lattice in radiation dose enhancement owing to its higher mass attenuation coefficient. Upon X‐ray or γ‐ray radiation, Th‐DBP enhanced energy deposition, generated more reactive oxygen species, and induced significantly higher cytotoxicity to cancer cells over the previously reported Hf‐DBP nMOF. With low‐dose X‐ray irradiation, Th‐DBP suppressed tumor growth by 88 % in a colon cancer and 97 % in a pancreatic cancer mouse model.