Simulation is a very useful tool in the design of the part and process conditions of high-pressure die casting (HPDC), due to the intrinsic complexity of this manufacturing process. Usually, physics-based models solved by finite element or finite volume methods are used, but their main drawback is the long calculation time. In order to apply optimization strategies in the design process or to implement online predictive systems, faster models are required. One solution is the use of surrogate models, also called metamodels or grey-box models. The novelty of the work presented here lies in the development of several metamodels for the HPDC process. These metamodels are based on a gradient boosting regressor technique and derived from a physics-based finite element model. The results show that the developed metamodels are able to predict with high accuracy the secondary dendrite arm spacing (SDAS) of the cast parts and, with good accuracy, the misrun risk and the shrinkage level. Results obtained in the predictions of microporosity and macroporosity, eutectic percentage, and grain density were less accurate. The metamodels were very fast (less than 1 s); therefore, they can be used for optimization activities or be integrated into online prediction systems for the HPDC industry. The case study corresponds to several parts of aluminum cast alloys, used in the automotive industry, manufactured by high-pressure die casting in a multicavity mold.