In order to assess the product quality and shelf life of an Italian soft cream cheese under different storage conditions, the volatile and peptide profiles evolution were tested. Volatiles were sampled directly from the head space of cheese packaging by solid-phase microextraction and analyzed by GC-MS. Peptide profiles were obtained by nanoLC-MS/MS, following a novel bioinformatics approach based on scoring distribution associated to the protein hits originating from the database search. In particular, a refined identification by focusing on selected time segments corresponding to the most intense peaks was carried out. A total of 40 compounds including acids, aldehydes, ketones, lactones, alcohols, esters, hydrocarbons, terpene, sulfur, and aromatic compounds were detected. Significant differences in their abundance during the storage in different packagings were observed, as well as an evolution of peptides mainly belonging to alpha S1-casein. The results demonstrated the usefulness of the above-mentioned hyphenated techniques for the determination of the soft cheese shelf life under different storage conditions.