Simulation techniques are powerful tools for determining the optimal conditions necessary for microwave ablation to be efficient and safe for treating liver tumors. Owing to the complexity and computational resource consumption, most of the existing numerical models are two-dimensional axisymmetric models that emulate actual three-dimensional cancers and the surrounding tissue, which is often far from reality. Different tumor shapes and sizes require different input powers and ablation times to ensure the preservation of healthy tissues that can be determined only by the full three-dimensional simulations. This study aimed to tailor microwave ablation therapeutic conditions for complete tumor ablation with an adequate safety margin, while avoiding injury to the surrounding healthy tissue. Three-dimensional simulations were performed for a multi-slot microwave antenna immersed in two tumors obtained from the 3D-IRCADb-01 liver tumors database. The temperature dependence of the dielectric and thermal properties of healthy and tumoral liver tissues, blood perfusion, and water content are crucial for calculating the correct ablation time and, thereby, the correct ablation process. The developed three-dimensional simulation model may help practitioners in planning patient-individual procedures by determining the optimal input power and duration of the ablation process for the actual shape of the tumor. With proper input power, necrotic tissue is placed mainly in the tumor, and only a small amount of surrounding tissue is damaged.