Saffron is well known for its use as a condiment spice, as a dye and in traditional medicine, but very little information is available on the relationship between agronomic management and the qualitative features of this spice, the latter strictly associated with its unique metabolic profile represented by the crocetin esters, picrocrocin and safranal. There is increasing interest in saffron because of its specific and multiple properties. The aim of this study was to evaluate the influence of climatic condition and genotype on compositional characteristics of saffron. Flower number and stigma yield were significantly affected by environment and corm provenance. The content of the main crocetin esters, namely trans-crocetin di-(²-d-gentibiosyl) ester (1), trans-crocetin (²-d-glucosyl)-(²-d-gentibiosyl) ester (2), trans-crocetin (²-d-gentibiosyl) ester (3), trans-crocetin (²-d-glucosyl) ester (4), and picrocrocin, were evaluated according to the spectrophotometric ISO standard methodology, which ranked the samples into three qualitatively decreasing categories (I–III); composition was evaluated mainly through the application of HPLC equipped with ultraviolet visible diode array detector and electro-spray mass spectrometer detectors (HPLC–UV–vis-DAD–ESI-MS), which made it possible to determine the metabolic profiles of stigma samples in terms of crocetin esters and picrocrocin content. The chemical data were combined with the environmental conditions and genotype, and the results showed that crocetin esters 1 and 2 represent the major components of total crocetin ester amount, as indicated by the high positive correlation (0.971 and 0.833, respectively). Moreover crocetin esters 2 and 4, and total crocetin esters amount resulted correlated with picrocrocin content (0.794, 0.818 and 0.678, respectively). Finally, a Pearson correlation was performed in order to individuate any possible relationship between yield characteristics (flower number, total yield and unitary stigma weight) and the qualitative parameters of saffron.