Waterflooding is one of the methods used for increased hydrocarbon production. Waterflooding optimization can be computationally prohibitive if the reservoir model or the optimization problem is complex. Hence, proxy modeling can yield a faster solution than numerical reservoir simulation. This fast solution provides insights to better formulate field development plans. Due to technological advancements, machine learning increasingly contributes to the designing and building of proxy models. Thus, in this work, we have proposed the application of the two-stage proxy modeling, namely global and local components, to generate useful insights. We have established global proxy models and coupled them with optimization algorithms to produce a new database. In this paper, the machine learning technique used is a multilayer perceptron. The optimization algorithms comprise the Genetic Algorithm and the Particle Swarm Optimization. We then implemented the newly generated database to build local proxy models to yield solutions that are close to the “ground truth”. The results obtained demonstrate that conducting global and local proxy modeling can produce results with acceptable accuracy. For the optimized rate profiles, the R² metric overall exceeds 0.96. The range of Absolute Percentage Error of the local proxy models generally reduces to 0–3% as compared to the global proxy models which has a 0–5% error range. We achieved a reduction in computational time by six times as compared with optimization by only using a numerical reservoir simulator.