T2DSystems will take advantage of very recent advances in technology and modelling approaches to integrate high-throughput experimentation with quantitative analysis, modelling and testing/validation to understand the dynamics of pancreatic beta cell failure in T2D. T2DSystems will thus address unsolved disease mechanisms, reveal system-level properties and processes, and gain a more comprehensive and fundamental understanding of T2D. T2DSystems will leverage existing investments in Europe in the field of systems biomedicine. Thus, we will exploit current developments of mathematical models applied to identify correlations between heterogeneous data types that can capture dependencies and associations between distant processes in relation to T2D predisposition, onset and progression. These correlations will be further explored, refined and interpreted using network and systems biology approaches based on known functional associations in order to identify key pathological pathways, molecular players and the disease mechanisms of potential clinical interest. It will provide new directions for improved T2D diagnosis, prevention and therapy, and generate systems medicine tools and approaches for T2D research and care. Taken together this multilevel approach will represent a significant step forward in the understanding and treatment of the different underlying T2D molecular mechanisms and a clear improvement over current practices and approaches, setting an important basis for the study of other complex chronic diseases.