In this paper, a systematic model-development strategy using model-based experimental design, consisting of initial data acquisition, model development, model identification, model validation and model refining, is developed. Model development is based on the reaction network proposed within the reaction supernetwork containing all feasible chemical reactions and mass transfers. For model identification, validation and refining, model-based experimental design is performed by taking into consideration several reactors, which enlarges the explored experimental windows. Based on this strategy, a computer-aided software, facilitating the user’s work, is developed for model development of liquid-phase reaction systems. The application of the strategy is demonstrated with an experimental case study involving NaOH-catalyzed ethanolysis of sunflower oil.