The MADNESS project aims at the definition of innovative system-level design methodologies for embedded MP-SoCs, extending the classic concept of design space exploration in multi-application domains to cope with high heterogeneity, technology scaling and system reliability. The main goal of the project is to provide a framework able to guide designers and researchers to the optimal composition of embedded MPSoC architectures, according to the requirements and the features of a given target application field. The proposed approach will tackle the new challenges, related to both architecture and design methodologies, arising with the technology scaling, the system reliability and the ever-growing computational needs of modern applications. The methodologies proposed with this project act at different levels of the design flow, enhancing the state-of-the art with novel features in system-level synthesis, architectural evaluation and prototyping. Support for fault resilience and efficient adaptive runtime management is introduced at hardware and middleware level, and considered by the system-level synthesis as one of the optimization factors to be taken into account. This paper presents the first stable results obtained in the MADNESS project, already demonstrating the effectiveness of the proposed methods.