With almost 70years of experience and 440 nuclear reactors in operation in 30 countries, nuclear energy provides 10% of the world's electricity and is the world's second largest carbon-free power. There is a clear need for new generating capacity around the world, both to meet increased demand for electricity in many countries, and to replace old fossil fuel units and transition to the use of low-carbon and carbon-free energy. Nuclear technology has a great potential to play a key role in the distant future to continue providing the world with a safe, reliable, economically competitive, and secure proliferation-resistant source of energy. Based on lessons learned from the OPerating EXperience (OPEX) of Nuclear Power Plants (NPPs) and prospective solutions for future energy production and environmental protection challenges, Generation-IV reactors have been developed with new innovative technological solutions to satisfy stringent regulatory requirements. As a result, over the last 10 or so years, there has been a recent surge in nuclear industry interest in the development of advanced Generation-IV reactors, including Small Modular Reactors (SMRs). Most of the proposed new designs use non-conventional cooling mediums, new, and advanced materials suitable for operating conditions such as high temperatures. Such combinations will likely create many new challenges for regulators and designers to determining reactor system and components Fitness-For-Service (FFS), like In-Service Inspection (ISI) challenges with graphite. Accordingly, the focus of this chapter is to initiate a discussion on regulatory status, requirements, and challenges related to the design and FFS of mechanical components, as well as to share the regulatory experience with a number of proposed SMR designs through the prelicensing vendor design review process in Canada. Some of these SMR designs propose to operate under relatively high neutron fluxes and at elevated temperatures to achieve high thermal efficiency compared with current operating power reactors. Other designs employ a highly corrosive cooling medium. Such operating conditions could accelerate or present unforeseen degradation mechanisms that could adversely affect the integrity and service life of the pressure boundary. Therefore, it is crucial to understand material behavior and identify plausible degradation mechanisms and damage modes by considering operating conditions in which SMRs are essential elements in order to ensure the structural integrity of Pressure Retaining Systems and Components (PRSC) over their design life.