This paper describes a collaborative project between the US, Ireland, and Northern Ireland (UK) to investigate advanced manufacturing cutting techniques for the creation of a new class of intermeshed steel connections that rely on neither welding nor bolting. To date, advanced manufacturing equipment has only been used to accelerate traditional processes for cutting sheet metal or other conventional fabrication activities. Such approaches have not capitalized on the equipment’s full potential. This project lays the groundwork to transform the steel building construction industry by investigating the underlying science and engineering precepts for intermeshed connections created from precise, volumetric cutting. The proposed system enhances the integration between design, fabrication, installation and maintenance through building information modeling platforms to implement advanced connections. Fully automated, precise, volumetric cutting of open steel sections introduces intellectual challenges regarding the load-transfer mechanisms and failure modes for intermeshed connections. The research activity addresses knowledge gaps concerning the load resistance and design of steel systems with intermeshed connections. Physical tests, finite element simulation and multi-scale modeling are being used to investigate the mechanics of intermeshed connections including stress and strain concentrations, fracture potential and failure modes, and to optimize connection geometry.