A closed-loop forward-inverse joint multi-layer temperature prediction method is introduced to overcome the limitations of non-contact microwave-based precise temperature measurements within human tissues. This approach merges an incoherent four-layer tissue forward model with a multi-frequency high-precision inversion algorithm. Random errors were incorporated into the forward model to construct a multi-layer human tissue dataset for performance validation and optimization of the inversion algorithm. The lack of precise temperature measurements in internal human tissues was addressed using an incoherent four-layer forward model that integrates the Pennes heat transfer equation with a fluid–solid coupling boundary modeling technique. Parameter differentiation analysis was conducted in the forward modeling step using incoherent electromagnetic transport equations. The proposed high-precision multi-frequency inversion process, added to the objective function, refines the XGBoost algorithm by assigning a penalty factor and adjusting for neighboring tissue temperature distributions. The Optuna framework was then utilized to optimize XGBoost hyper-parameter sets, resulting in the Opt-XGBoost inversion algorithm. This approach achieved a root mean square error of 0.033 °C and an average absolute error of 0.0256 °C in simulations involving forward modeling-generated data.