Understanding the intracellular fate of nanoparticles (NPs) is critical for advancing nanomedicine, particularly in targeted drug delivery for cancer therapy. Here, we present a multimodal cryogenic microscopy workflow (correlative light, electron, and X-ray microscopy- CLEXM) to investigate the uptake and subcellular localization of zirconyl-containing inorganic-organic hybrid nanoparticles (IOH-NPs) in murine breast cancer cells. Our approach integrates cryogenic fluorescence microscopy (cryo-FM), cryo-focused ion beam scanning electron microscopy (cryo-FIBSEM), and cryo-soft X-ray tomography (cryo-SXT), enabling molecular specificity, high-resolution imaging, and volumetric ultrastructural analysis in near-native cellular states. We demonstrate that the cryogenic workflow provides enough contrast and resolution across all modalities for quantifying the IOH-NP uptake: NPs are internalized within two hours of incubation and progressively accumulate in endolysosomes over time, as confirmed by fluorescence labeling and SXT. Quantitative analysis reveals a marked increase in endolysosomal accumulation of IOH-NPs from 2 to 24 hours. Our findings help to establish multimodal cryogenic microscopy as a powerful tool for nanoscale imaging and quantitative analysis of NP uptake within close-to-native cells, offering new insights into NP trafficking and cellular responses relevant to nanomedicine development.