This Zenodo record contains the fine-tuned Cellpose-SAM model weights for cell and nucleus segmentation in serial block-face scanning electron microscopy (SBF-SEM) images of tumor spheroids, as described in: Bottone et al., 3D Reconstruction of Nanoparticle Distribution in Tumor Spheroids with Volume Electron Microscopy Two models are provided, targeting cells and nuclei respectively. Both were fine-tuned from the pretrained Cellpose-SAM baseline on manually annotated SBF-SEM images of FaDu head-and-neck carcinoma spheroids resampled to isotropic 100×100×100 nm voxel spacing. Each model folder contains the model weights alongside the training configuration (config.json) and training manifest (training_manifest.json) for full reproducibility. The models can be loaded and used directly via the sphero-vem library (https://github.com/dv-bt/sphero-vem) or the standard Cellpose API. The annotated training dataset is available at BioImage Archive (https://doi.org/10.6019/S-BIAD3263).