This paper presents a framework for automated optimization of double-heater convective PCR (DH-cPCR) devices by developing a computational fluid dynamics (CFD) simulation database and artificial neural network (ANN) model. The optimization parameter space that includes the capillary tube geometries and the heater sizes of DH-cPCR is established, and a database consisting of nearly 10,000 CFD simulations is constructed. The database is then used to train a two-stage ANN models that select practically relevant data for modeling and predict PCR device performance. The trained ANN model is then combined with the gradient-based and the heuristics optimization approaches to search for optimal device configuration that possesses the shortest DNA doubling time. The entire design process including model meshing and configuration, parallel CFD computation, database organization, and ANN training and utilization is fully automated. Case studies confirm that the proposed framework can successfully find the optimal device configuration with an error of less than 0.3 s, and hence, representing a cost-effective and rapid solution of DH-cPCR device design.