High-throughput native mass spectrometry (HT-nMS) is an emerging technique increasingly used for hit identification in drug discovery applications by providing rapid, sensitive, and accurate analysis of biomolecular interactions and conformational states of protein-ligand complexes. Unlike traditional methods, HT-nMS allows for the direct observation of non-denaturing protein-ligand complexes, enabling the assessment of binding affinities, stoichiometries, and kinetic parameters in their native states. This presentation will explore the integration of HT-nMS into hit identification workflows, outlining the instrumentation, sample preparation and initial proof of concept results. Through its ability to characterize complex biomolecular systems in a high-throughput format, HT-nMS is poised to accelerate the drug discovery process and drive the development of next-generation therapeutics.