Background: 90Y and 177Lu are two well-known radionuclides used in radionuclide therapy to treat neuroendocrine tumors.Objective: This current study aims to evaluate, compare and optimize tumor therapy with 90Y and 177Lu for different volumes of the tumor using the criterion of self-absorbed dose, cross-absorbed dose, absorbed dose profile, absorbed dose uniformity, and dose-volume histogram (DVH) curve using Gate Monte Carlo simulation code. Material and Methods: In our analytical study, Gate Monte Carlo simulation code has been used to model tumors and simulate particle transport. Spherical tumors were modeled from radius 0.5 to 20 mm. Tumors were uniformly designed from water (soft tissue reagent). The full energy spectrum of each radionuclide of 177Lu and 90Y was used in the total volume of tumors with isotropic radiation, homogeneously. Self-absorbed dose, cross-absorbed dose, absorbed dose profile, absorbed dose uniformity, and DVH curve parameters were evaluated. Results: The absorbed dose for 90Y is higher than 177Lu in all tumors (p-value <5%). The uniformity of the absorbed dose for 177Lu is much greater than 90Y. As the tumor size increases, the DVH graph improves for 90Y. Conclusion: Based on self-absorbed dose, cross-absorbed dose, absorbed dose uniformity, and DVH diagram, 177Lu and 90Y are appropriate for smaller and larger tumors, respectively. Next, we can evaluate the appropriate cocktail of these radionuclides, in terms of the type of composition, for the treatment of tumors with a specific size.