[Methods in Mol. Bio.] Mass spectrometry (MS)-based strategies have emerged as key elements for structural modelling of proteins and their assemblies. In particular, merging together complementary MS tools, through the so-called hybrid approaches, have enabled structural characterization of proteins in their near native states. Here, we describe how different MS techniques, such as native MS, chemical cross-linking MS and ion mobility MS, are brought together using sophisticated computational algorithms and modelling restraints. We demonstrate applicability of the strategy by building accurate models of multimeric protein assemblies. These strategies can practically be applied to any protein complex of interest and be readily integrated with other structural approaches such as electron density maps from cryo-electron microscopy.