MARIO (Multi-Regional Analysis of Regions through Input-Output) is a Python-based framework for building input-output models. It automates the parsing of well-known databases (e.g. EXIOBASE, EORA, Eurostat) and of customized tables. With respect to similar tools, like pymrio, it broadens the scope of application to supply-use tables and handles both monetary and physical units. Employing an intuitive Excel-based API, it facilitates advanced table manipulations and allows for modelling additional supply chains through a hybrid LCA approach. It provides built-in functions for footprinting and scenario analyses as well as for visualizations of model outcomes. Results are exportable into various formats, possibly supplemented by a metadata file tracking the full history of applied changes. MARIO comes with extensive documentation and is available on Zenodo, GitHub, or installable via PyPI.