We present Vertiport-informed Surrogate-Based Optimization with Machine Learning Surrogates (VinS), a novel framework for solving the vertiport location problem for urban air mobility operations. The primary focus of this work is on the optimization of vertiport locations to facilitate efficient urban air transportation. Our framework helps choose not only the optimal vertiport locations but also the optimal number of vertiports. We develop a simulation model to analyze the impacts of various vertiport location configurations on the efficiency of the transportation network. To expedite the simulation process, a surrogate model is trained using machine learning algorithms, effectively reducing the computational time for evaluating a given vertiport location configuration. With the machine learning surrogate models, we apply a genetic algorithm to find the optimal set of vertiport locations. An empirical study was performed in the San Francisco Bay Area, from which we found that given the optimal set of vertiport locations, we further reduced the total travel time in the entire transportation system in the Bay Area compared with the sampled sets by 0.05% (400 h) on average. We release our framework at: https://github.com/Xuan-1998/LPSim .