In cancer treatment, laser ablation is a promising technique used to induce localized thermal damage. Different variables influence the temperature distribution in the tissue and the resulting therapy efficacy; thus, the optimal therapy settings are required for obtaining the desired clinical outcome. In this work, thermomechanical modeling of contactless laser ablation was implemented to analyze the sensitivity of independent variables on the optimal treatment conditions. The Finite Element Method was utilized to solve the governing equations, i.e., the bioheat, mechanical deformation, and the Navier-Stokes equations. Validation of the model was performed by comparing experimental and simulated temperatures, which indicated high accuracy for estimating temperature. In particular, the results showed that the model can estimate temperature with a good correlation factor (R = 0.98) and low Mean Absolute Error (3.9 °C). A sensitivity analysis based on laser irradiation time, power, beam distribution, and the blood vessel depth on temperature distribution and fraction of necrotic tissue was performed. An optimization process was performed based on the most significant variables, i.e., laser irradiation time and power. This resulted in an indication of the optimal therapy settings for achieving maximum procedure efficiency i.e., the required fraction of necrotic tissue within the target volume, constituted by tumor and safety margins around it.