A variety of Generation III/III+ reactor designs featuring enhanced safety and improved economics are being proposed by nuclear power industries around the world to solve the future energy supply shortfall. Nanofluid coolants showing an improved thermal performance are being considered as a new key technology to secure nuclear safety and economics. However, it should be noted that there is a lack of comprehensible design works to apply nanofluids to Generation III+ reactor designs. In this work, the review of accident scenarios that consider expected nanofluid mechanisms is carried out to seek detailed application spots. The Axiomatic Design (AD) theory is then applied to systemize the design of nanofluid-engineered nuclear safety systems such as Emergency Core Cooling System (ECCS) and External Reactor Vessel Cooling System (ERVCS). The various couplings between Gen-III/III+ nuclear safety features and nanofluids are investigated and they try to be reduced from the perspective of the AD in terms of prevention/mitigation of severe accidents. This study contributes to the establishment of a standard communication protocol in the design of nanofluid-engineered nuclear safety systems.