The development of new engineering alloy chemistries and heat treatments is a time-consuming and iterative process. Here, a hybrid approach of the high-throughput precipitation simulations and decisive experiments is developed to optimize the composition and manipulate the microstructure of Al-Zn-Mg-Cu alloys to achieve the expected yield strength and elongation. For that purpose, a multi-class Kampmann-Wagner numerical (KWN) framework is established and the contributions to precipitation kinetics and strength from primary phases and precipitates formed before age hardening are introduced for the first time. The composition/process-structure-property relationship of Al-Zn-Mg-Cu alloys is presented and discussed in detail. Coupled with thermodynamic calculations, two concentration-optimized Al-Zn-Mg-Cu alloys with expected high yield strength and long elongation are designed, prepared, and characterized. The excellent strength and elongation of the designed alloys and the good agreement between the measured and model-predicted mechanical properties for these two alloys underscores the remarkable predictive power of the presently developed material design strategy. This work establishes a novel material design strategy for rapidly exploring the compositional space and investigating the effects of composition and heat treatment on the microstructure and performance of ultrahigh strength Al alloys and other materials.