This manuscript presents important material challenges regarding innovative Gen-II/III nuclear systems and research reactors. The challenges are discussed alongside the key achievements so far realised within the framework of 4 EU-funded projects: H2020 IL TROVATORE, FP7 MULTIMETAL, FP7 MATTER and FP7 SCWR-FQT. All the four Projects deal with innovative researches on materials to enhance the safety of nuclear reactors. IL TROVATORE proposes new materials for fuel cladding of PWR reactors and tests in order to really find out an “Accident Tolerant Fuel” (ATF). MULTIMETAL focused on optimization of dissimilar welds fabrication having considered the field performances and dedicated experiments. MATTER carried on methodological and experimental studies on the use of grade 91 steel in the harsh environment of liquid metal cooled EU fast reactors. SCWR-FQT focused on fuel qualification of Supercritical Water Reactor including the selection of the better material to resist the associated high thermal flux.