Problems about future energy availability, climate changes, and air quality seem to play an important role in energy production. While current reactor generations provide a guaranteed and economical energy production, new nuclear power plant generation would increase the ways and purposes in which nuclear energy can be used. To explore these new technological applications, several governments, industries, and research communities decided to contribute to the next reactor generation, called “Generation IV.” Among the six Gen-IV reactor designs, the Gas Cooled Fast Reactor (GCFR) uses a direct-cycle helium turbine for electricity generation and for a CO2-free thermochemical production of hydrogen. Additionally, the use of a fast spectrum allows actinides transmutation, minimizing the production of long-lived radioactive waste in an integrated fuel cycle. This paper presents an analysis of GCFR fuel cycle optimization and of a thermal-hydraulic of a GCFR-prototype under steady-state and transient conditions. The fuel cycle optimization was performed to assess the capability of the GCFR to transmute MAs, while the thermal-hydraulic analysis was performed to investigate the reactor and the safety systems behavior during a LOFA. Preliminary results show that limited quantities of MA are not affecting significantly the thermal-fluid-dynamics behavior of a GCFR core.