The growing global demand for mineral resources is challenging mining operations to maintain productivity while addressing lower-grade ore and increased extraction complexity. Despite the availability of vast datasets across mining stages, much of this information remains underused in decision-making. This study presents an integrated, knowledge-based framework that leverages artificial intelligence (AI) and high-fidelity simulation to model and optimise the full mine to mill process. Using publicly available data from the Barrick Cortez Mine in Nevada, USA, the mining chain from blasting to semi-autogenous grinding (SAG) was modelled using the Integrated Extraction Simulator (IES) from Orica. To mitigate the computational burden of full factorial simulations, three million scenarios were generated to evaluate performance sensitivity. Machine learning models, including linear regression, decision trees, random forests, and XGBoost, were trained and validated. The models achieved an accuracy of more than 90%, underscoring their reliability for predicting process outcomes. SHapley Additive exPlanations (SHAP) were applied to interpret model predictions and quantify feature importance. The findings confirm a strong alignment between simulation and real-world data and highlight key operational parameters that affect downstream process performances. This meta-model approach offers a powerful tool for real-time decision-making, enabling mining operations to improve efficiency, reduce costs, and support sustainable resource management.