This paper introduces the use of structural topology optimization (TO) as a new design approach that enables the creation of monolithic load-bearing cast glass components of substantial dimensions with significantly reduced annealing times, rendering such components viable in terms of manufacturing. Using topology optimization, the glass mass can be optimized to match design loads whilst maintaining high stiffness and a homogeneous mass for even cooling. Initially, the two main TO approaches are discussed in terms of suitability for cast glass. A strain-based optimization is eventually preferred over Von Mises optimization in the specific study. To explore the potential of TO for optimizing structural cast glass components, three distinct studies are analyzed in ANSYS workbench: (i) a structural glass node, (ii) a cast glass floor and (iii) a pedestrian bridge. These lead to the establishment of a set of design/input criteria, taking into account glass as a material, casting as a manufacturing method, addressing also the safety of the structure. The design studies also reveal the inherent challenges of using TO for load-bearing glass components, which, in turn, lead to the establishment of design guidelines for developing a TO tool specifically for glass. Towards the real-life applicability of such complex-shaped, customized components, possible manufacturing methods are also discussed.