This article presents a novel design optimization method for hybrid-powered multirotor unmanned aerial vehicles (HPUAVs) to enhance flight endurance and performance. Conventional multirotor unmanned aerial vehicles (UAVs) encounter restricted flight endurance due to battery capacity limitations and the lack of aerodynamic benefits. Furthermore, enhancing payload capacity for diverse missions presents a complex and demanding challenge. To overcome these challenges, a hybrid power system (HPS) incorporating an internal combustion engine and a generator has been developed. The HPUAV can harness in-flight power generation to optimize both flight endurance and payload capacity. However, the design procedure is challenging due to constraints related to compact dimensions and weight restrictions. This article establishes a design framework for multi-objective optimization with mathematical models of the principal components for HPUAVs. Analytical models of each component are established to evaluate the performance of the propulsion system and the HPS. Then, two multiple-objective optimization methods are applied to find the Pareto front exploring design objectives. The feasibility of the formulated design problem is demonstrated through experimental comparisons of optimal design candidates for two different sizes of HPUAVs. The results show that the optimization design method in this article can provide an effective means to design various-sized HPUAVs for a range of missions and diverse applications.