Irradiation is a non-thermal technique used for food preservation and sanitization to prolong shelf life and prevent spoilage. In this work, the X-ray irradiation treatment was applied to a highly appreciate soft cheese in Italy, i.e. Robiola cheese, produced from cow milk. The quality-type fingerprint of X-ray irradiated Robiola was characterized using HS-SPME combined with GC-MS to study the possible radio-induced modifications. A design of experiments approach based on a full factorial design and a central composite design for response surface methodology was used to optimize HS-SPME procedure. The resulting setting parameters were used to investigate irradiated samples at three dose levels (1.0, 2.0, 3.0 kGy), and considering three intervals post-treatment (immediately after irradiation, one month and two months later). The results highlighted alterations in the volatile profile of the cheese after irradiation, with production of other volatiles, such as seven alkanes, five alkenes, two alcohols, four aldehydes and four esters already at 1.0 kGy. Alcohols, aldehydes and esters were particularly affected by irradiation and shelf life, potentially due to lipid and protein oxidation processes. No migration of molecules from the packaging and no production of unknown volatiles were observed in irradiated samples during the monitoring period. Principal component analysis, partial least square discriminant analysis and artificial neural networks were employed to discriminate cheese samples based on irradiation and storage time. The results confirm the proposed analytical workflow as a useful tool to verify the X-ray irradiation, the time elapsed from the treatment and the labelled shelf life.