This paper examines the frequency response function (FRF) of a sealed spent nuclear fuel canister subjected to external excitation, focusing on the identification of potential damage scenarios such as canister misloading. Variations in FRFs are investigated through a combination of high-fidelity finite element modeling and experimental analysis using a mock-up of a fully loaded canister-basket system. A novel methodology for FRF computation is introduced, leveraging dynamic model reduction techniques to enhance computational efficiency. Experimental investigations utilize a modal shaker to induce vibrations in the canister, with acceleration responses measured at multiple locations under varying conditions. The study highlights the advantages of the nested Craig-Bampton method in reducing computational complexity while maintaining accuracy. Hypothetical damage cases, such as missing fuel assemblies, are effectively localized in both numerical simulations and experimental setups using the proposed framework. Findings demonstrate that dynamic vibration measurements on the external shell of the canister can reliably detect physical abnormalities, offering a non-invasive diagnostic tool for spent nuclear fuel packages. This work underscores the potential of combining advanced finite element modeling and experimental modal analysis to enhance the safety and reliability of nuclear fuel storage systems.