Façades represent complex and vulnerable components for buildings, due to the intrinsic fragility and brittleness of glass, and require specific design and calculation tools, both for ordinary and extreme design loads. In this context, the availability of consolidated and strategic modelling strategies is of utmost importance for structural safety considerations and optimal decisions. In this paper, the attention is focused on the assessment of different modelling strategies for the global and local behaviour analysis of Glass Curtain Walls (GCWs) under in-plane seismic loads. Benefits and limitations are discussed for a more refined (but expensive, “MREF”) and a simplified (and computationally efficient, but weak in capturing local phenomena, “MSIMP”) model assemblies developed in ABAQUS and SAP2000, respectively. Careful consideration is given for typical mechanisms, local responses, key performance indicators for the façade components (i.e., stress and deformation peaks) for a reference GCW under monotonic and cyclic loads, as well as for major effects due to general input parameters (i.e., contact mechanisms, clearance, friction, bare frame features, secondary components, etc.), based on a parametric sensitivity investigation. The parametric comparative results are critically discussed, with the support of an experimental prototype test from literature, and the most influencing parameters are emphasized, to improve and facilitate the development of further design and modelling optimization strategies.