The feasibility of using optical coherence tomography, a label-free, non-invasive technique, to monitor three-dimensional (3D) morphology and pathology of tumor spheroids has been previously demonstrated. Growth kinetics of each spheroid, with its size and volume measured, could be accurately characterized. However, the previous system was not fully optimized for the collection of spheroid data from the whole plate. Here, in a follow-up study, we demonstrated a high-throughput optical coherence tomography (HT-OCT) platform capable of performing automatic 3D imaging and analyses for all tumor spheroids in a multi-well plate. The total screening time for a 96-well plate was ~23 min, including the OCT acquisition time of ~3.2min. Employing HT-OCT system, we successfully characterized a plate of tumor spheroids modeling cell invasions, with 3 different drug treatments. The HT-OCT system can be a powerful tool for fast, robust 3D morphological characterization of simple and complex spheroids for different cancer models. Further, they can also be utilized to analyze other models like organoids and artificial skins.