Synergetic transportation schemes are extensively used in package delivery operations, exploiting the best features of different modes. This paper proposes a methodology to solve the mode assignment and routing problem for the case of combined conventional vehicle and unmanned aerial vehicle (CV–UAV) parcel deliveries under uncertainty for next-day operations. This research incorporates ground and air uncertainties: travel times are assumed for conventional vehicles, while UAV paths are affected by weather conditions and restricted flying zones. A nested genetic algorithm is initially used to solve the problem under fixed conditions. Then, a robust optimization approach is employed to propose the best solution that will perform well in a stochastic environment. The framework is applied to a case study of realistic urban–suburban size, and results are discussed. The entire platform is useful for strategic decisions on infrastructure and for operation planning with satisfactory performance and less risk.