Over recent years materials with a high density of nanoscale interfaces are finding increasing attention due to their improved radiation tolerance in comparison to their bulk form. The efficient trapping and recombination of radiation induced point defects such as vacancies and interstitials at such interfaces are proposed to be the fundamental reason for their increased radiation tolerance. Several different ODS steels, nanostructured ceramic materials and nanolayered thin films have been recently investigated to understand the fundamental mechanism of radiation damage. In many of these investigations high energy He ion irradiations were carried out in a large area over the entire specimen followed up with characterization of radiation damage. The spot size of ion irradiation beams from conventional sources was in the order of 100s of microns or larger preventing a site specific irradiation damage investigation of individual microstructural features. In such cases often the overall irradiation damage evolution in the material would be a cumulative response of the entire material microstructure (grain boundaries, interphase-interfaces, second phase precipitates and other preexisting defects) to the ion beam irradiation. A nanoscale site specific He ion irradiation method, if made possible can aid in decoupling and individually analyzing the He ion irradiation response of different microstructural features in a mutually exclusive manner. He ion microscopy (HIM) developed in recent years offer such a capability for obtaining coherent He ion beams that can be precisely controlled and directed to areas as small as few nanometers. In EMSL, a DOE national user facility in PNNL, efforts are underway to look at irradiation response of nanoscale microstructural features in nanolayered metallic thin films by cross coupling site specific He ion irradiations with site specific TEM and Atom probe tomography (APT) sample preparation methods made possible by Focused ion beam system. Proof of principle experiments are being conducted in nanoscale PVD synthesized Ti/Al nanolayer thin films using He ion irradiation doses ranging from 1E14 to 1E17 ions/cm2 and subsequent analysis by TEM and APT. Recent results from this study will be presented in this paper.