This work develops a rule curve-based conjunctive use management model for optimizing the operating rules for a lake-groundwater system with off-stream storage lakes. The proposed procedure is a simulation-optimization approach that embeds an Artificial Neural Network (ANN) instead of a groundwater numerical model into a genetic algorithm (GA). The direct physical exchange between lake water with groundwater is simulated using the ANN model, which is a reduced version of a full numerical model, MODFLOW with an LAK3 module. By applying the ANN model, the proposed procedure can reduce the computational burden that is induced by the nonlinear exchange. An operating rule-based optimal conjunctive use management model for the Gaopin Artificial lakes system in Taiwan was thus developed using the proposed framework. A set of optimal solutions involves rule curves and a discount ratio. Simulation results demonstrate that the embedded ANN model can accurately simulate the nonlinear exchange of a lake with groundwater. The embedded ANN model is less computationally complex than the numerical model. This work demonstrates a methodology for reducing the computational burden of the optimal conjunctive use management model that is associated with an internal nonlinear system by using the ANN reduced model. Specifically, the concept of, and results obtained using the developed operating rule-based model incorporating five artificial lakes and considering the nonlinear exchange of those lakes with the groundwater system provides a valuable practical reference for solving related conjunctive use problems.