Novel treatment options and associated personalised, patient-tailored therapies need to be explored and developed for highly heterogeneous and chemotherapy resistant cancers, such as malignant melanoma. This can only be achieved by industry-academia collaborations in newly emerging, innovative research disciplines such as translational cancer systems biology and systems medicine. These disciplines and the associated European training needs provide the foundation for the MEL-PLEX ETN. MEL-PLEX aims to understand the network-level and multi-scale regulation of disease-relevant signalling in melanoma through a combination of quantitative biomedical and computational research approaches that go significantly beyond the current state-of-the-art. Coordinated by the RCSI Centre for Systems Medicine, MEL-PLEX will train 15 early stage researchers through a highly interdisciplinary and intersectoral research training programme. MEL-PLEX comprises 11 beneficiaries and 7 partner organisations from 11 countries, including European and international leaders in personalised melanoma therapy, melanoma systems biology and cancer systems medicine. MEL-PLEX aims to (i) achieve an unmatched depth of molecular and mechanistic disease understanding, (ii) will exploit this knowledge to develop and validate predictive models for disease progression, prognosis and responsiveness to current and novel (co-)treatment options, and (iii) will provide superior and clinically relevant tools and biomarker signatures for personalising and optimising melanoma treatment. The MEL-PLEX ETN addresses current needs in academia and the private sector for researchers that have been trained in an environment that spans across biology, medicine and mathematics, that can navigate confidently between clinical, academic and private sector research environments, and that have developed an innovative and creative mindset to progress research findings towards applications.