The limitations of conventional cancer therapies, such as low selectivity and significant side effects, necessitate innovative approaches. This study proposes a pioneering self-theranostic strategy using magnesium-28 (Mg-28) alone, enabling simultaneous diagnosis, therapy, and treatment monitoring. Exploiting the elevated Mg ion demand in cancer cells, Mg-28 selectively targets Mg-dependent enzymes (e.g., DNA/RNA polymerases, hexokinase, telomerase) within intracellular organelles, such as the nucleus and mitochondria, without requiring biochemical carriers or nanoparticles, as in recent methods. A theoretical model based on the Mg-uptake coefficient predicts selective Mg-28 accumulation in tumors following intravenous administration. The Mg-28 decay chain—progressing through Aluminum-28 to stable Silicon-28—delivers highly localized irradiation through beta particles, Auger electrons, and recoil ions to critical intracellular structures, while simultaneously disrupting essential Mg-dependent enzymes. This results in a dual mechanism of radiotherapy and multi-enzyme inactivation. Simulations of linear energy transfer, radiation range, and absorbed dose show that nanogram-scale amounts of Mg-28 can deliver 60–400 Gy to tumors ranging from 0.03 mg to 500 g, suggesting potent cytotoxicity across a broad range of tumor sizes and stages. This potential is grounded in the universal metabolic reliance of cancer cells on Mg. Moreover, gamma emissions from Mg-28 and its daughter isotopes support early tumor detection and real-time treatment monitoring, enhancing therapeutic precision. As the first proposed single-isotope theranostic approach leveraging Mg dependency, this innovative strategy provides a robust foundation for future pre-clinical and clinical investigations aimed at validating its therapeutic efficacy, pharmacokinetics, and biosafety—thereby inaugurating a novel hypothesis for cancer therapy.