Nanoporous metals (np-metals) are a class of functional materials characterized by a bicontinuous network of nanoscale pores and solid ligaments, forming an open-cell porous structure. Their mechanical properties benefit from nanoscale effects, leading to enhanced performance. However, modelling the mechanical behaviour of np-metals remains challenging due to their complex topology. Various computational techniques have been employed, spanning multiple length scales—from molecular dynamics with realistic topologies to finite element simulations with idealized unit cells. Despite significant contributions to understanding their mechanical properties, the influence of topology and crystalline orientation on the plastic anisotropy of np-metals remains largely unexplored. In this contribution, we present a systematic assessment of the effects of topology and crystalline orientation on the plastic response of nanoporous gold (np-Au) under multiaxial loading. We employ a levelled-wave open-source code to generate np-Au representative volume elements (RVEs) with varying solid fractions and crystalline orientations. Multiaxial loading simulations are performed by means of a Crystal Plasticity Fast-Fourier Transform framework. Comparison with polycrystalline realizations as well as with an isotropic J2 plasticity model allow to distinguish the contributions of topology and crystallographic orientation to plastic deformation. Finally, our key findings are compared with existing contributions from other simulation techniques.