Nacre‐inspired Brick‐and‐Mortar composite structures exhibit exceptional combinations of properties as well as a highly tunable mechanical response, owing to their large range of design parameters. Understanding the effect of these parameters on the response is essential to optimally design these structures, and this can most efficiently be achieved through modelling. While many computational approaches have been proposed to investigate the relationships between the 2D (planar) geometric design parameters and the response of the structure, there have been limited attempts at modelling 3D (non‐planar) geometric designs. This is mainly due to the high computational cost associated with their complex shapes, including the soft, thin interfacial layer. In this work, we propose to model 3D Brick‐and‐Mortar structures using a finite element framework in conjunction with an experimentally calibrated Cohesive Zone Model to model the layers. The model is successfully validated against experimental results for a non‐planar brick assembly using so‐called osteomorphic bricks. The capabilities of the model are further demonstrated through a parametric study, where the effect of brick shape, number of bricks, and soft layer material properties on the structure mechanical properties (elastic modulus, yield strength and toughness) are investigated. In particular, our numerical results show that toughness is significantly increased by transitioning from a “two‐peak” failure mechanism to a “peak‐plateau‐peak”, which is mainly controlled by the brick shape (angle and aspect ratio). We also show that 3D structures may exhibit significant out‐of‐plane deformation involving the cooperative motion of many bricks, which may contribute to their improved toughness compared to 2D structures.This article is protected by copyright. All rights reserved.