Purpose <p>This study compares the subcellular dosimetry of ¹⁶¹&#xa0;Tb and ¹⁷⁷Lu, focusing on β⁻ particles, conversion electrons, and Auger electrons, and their relative contributions to cellular and subcellular damage. We aim to evaluate whether the higher emission yields of ¹⁶¹&#xa0;Tb provide a therapeutic advantage, particularly for non-internalizing targeting agents in radiopharmaceutical therapy.</p> Methods <p>A stochastic radionuclide decay model was implemented in MATLAB, incorporating internal conversion and Auger cascades and validated against ICRP 107. Geant4 track code simulations modeled electron transport in single-cell and voxelized membrane geometries. Energy deposition was assessed in the membrane, cytoplasm, and nucleus for 10,000 decays of each radionuclide.</p> Results <p>¹⁶¹&#xa0;Tb achieved similar nuclear energy deposition as ¹⁷⁷Lu with about 25% of the decays, due to its higher yield of internal conversion. These conversion electrons contribute to nuclear damage playing a crucial role in cell damage. Auger electrons from ¹⁶¹&#xa0;Tb additionally produced highly localized energy deposition at the cell membrane, that could also contribute to cell death. However, when normalizing for equivalent radiotoxicity to the bone marrow, around 75% of the ¹⁶¹&#xa0;Tb decays provide a similar marrow absorbed dose as ¹⁷⁷Lu, while still increasing the absorbed dose to the nucleus by approximately 18%.</p> Conclusion <p>¹⁶¹&#xa0;Tb offers a more efficient subcellular energy deposition profile than ¹⁷⁷Lu. It enables either similar therapeutic effect with fewer decays or enhanced nuclear absorbed dose under equivalent bone marrow toxicity. These results support the use of ¹⁶¹&#xa0;Tb in targeted radiopharmaceutical therapy, particularly for isolated tumor cells and micrometastases.</p>