Finally, despite the high level of heterogeneity, the systemic bioinformatics approach that we followed, based on the integration and correlation of different biologically informative layers, allowed us to evaluate the phenotypic melanoma state of tumours, highlighting transcriptional programmes and master regulators, such as MITF, NGFR, AXL, and SOX10, acting as driving forces that permit, or not, a cell population to switch from one state to another, defining tumour progression and aggressiveness with a direct impact on melanoma progression and anti-cancer drug resistance. Here, MITF is linked to melanoma.