A common goal for materials employed in nuclear environments is to exhibit the highest radiation tolerance. The lifetimes of current and even more of future reactors are largely determined by materials issues such as embrittlement and swelling. In the process of energy production via fission and fusion, structural materials are subject to substantial radiation damage, which appears in the form of point defects and their agglomeration to form dislocation loops and vacancy clusters. Combination of vacancy clusters with transmutation products such as helium (He) promotes the formation of He bubbles. These bubbles cause swelling, embrittlement and dimensional instabilities in structural metals, which represent a real challenge for application of metals in nuclear industry. It is well known that surfaces, grain boundaries and heterointerfaces are good sinks for radiation-induced point defects and traps for implanted He. Composite materials with a high interface density distribution showed enhanced radiation tolerance compared to conventional single phase metals. In spite of this beneficial effect, the role of He bubbles on the mechanical properties and structural integrity of nanostructured materials is still to be understood. This study is aimed at evaluating and correlating the effects of He bubbles formation with structural and mechanical properties of nanomaterials with high interface density distributions such as nanoscale metallic multilayers. With this aim, Cu/W multilayers were deposited by magnetron sputtering and subjected to He ion implantation (1 MeV) with two different fluences (1.1 and 3.2 ×1016 cm-2) and incident angles. Structure of pristine and irradiated multilayers was investigated by XRD and FIB/TEM analyses, while mechanical properties changes were evaluated by nanoindentation, through which possible deformation mechanisms in multilayers with He bubble-decorated interfaces were also investigated. By combining calculated He concentration profiles, throughout the multilayer thickness and TEM images, it is found that in low He concentrations regions, bubbles formed mostly along interfaces, while more homogeneously distributed bubbles were found in Cu layers and along columnar grain boundaries in higher He concentrations regions. It is suggested that the capability of interfaces to annihilate point defects is weakened by the He bubbles shielding effect. Nanoindentation tests revealed a hardness decrease amounting to ~ 0.5 and ~ 1 GPa for low and high fluences, respectively. The observed softening effect is mostly attributed to He storage induced changes in residual stresses, and columnar grain boundary sliding facilitated by He bubbles. <br/