Nanolaminates are extensively studied due to their unique properties, such as impact resistance, high fracture toughness, high strength, and resistance to radiation damage. Varieties of nanolaminates are being fabricated to achieve high strength and fracture toughness. In this study, one such nanolaminate fabricated through accumulative roll bonding (Cu(16)/Nb(16) ARB nanolaminate, where 16 nm is the layer thickness) was used as a test material. Cu(16)/Nb(16) ARB nanolaminate exhibits crystallographic anisotropy due to the existence of distinct interfaces along the rolling direction (RD) and the transverse direction (TD). Nanoindentation was executed using a Berkovich tip, with the main axis oriented either along TD or RD of the Cu(16)/Nb(16) ARB nanolaminate. Subsequently, height profiles were obtained along the main axis of the Berkovich indent for both TD and RD using scanning probe microscopy (SPM), which was later used to estimate the pile-up along the RD and TD. The TD exhibited more pile-up than the RD due to the anisotropy of the Cu(16)/Nb(16) ARB interface and the material plasticity along the TD and RD. An axisymmetric 2D finite element analysis (FEA) was also performed to compare/validate nanoindentation data, such as load vs. displacement curves and pile-up. The FEA simulated load vs. displacement curves matched relatively well with the experimentally generated load–displacement curves, while qualitative agreement was found between the simulated pile-up data and the experimentally obtained pile-up data. The authors believe that pile-up characterization during indentation is of great importance to documenting anisotropy in nanolaminates.