It is overall estimated that more than 12,000 people in the USA are diagnosed with a neuroendocrine tumor (NET) each year. POPEYE project uses advanced computational tools for the optimization of midgut MNETs treatment, towards the personalization of 177Lu-DOTA-peptide therapeutic protocols. An interdisciplinary approach exploits established tools and novel developments to increase the early, effective diagnosis, and the efficacy of 177Lu-DOTA-peptide radionuclide therapy. Clinical data are used to optimize the quantification on SPECT/PET acquisitions and accurately extract tumor radiomics. Monte Carlo simulations, incorporating Machine Learning techniques, serve as gold standard and allow dosimetry estimation on personalized treatment protocols. POPEYE’s ultimate goal is the clinical evaluation and exploitation of the proposed software & hardware tools to assess personalized MNETS diagnosis and therapy protocols. The multidisciplinary experience of the consortium members (Greece, France, Austria) ensures the efficient implementation of the project.