The development of commercial fusion power plants and Gen-IV fission reactors has been hindered by serious material challenges, including the low performance of available materials in extreme temperatures, radiation, and corrosive environments. High-entropy alloys (HEAs) have emerged as promising candidates for these applications because of their superior mechanical properties, radiation tolerance, and corrosion resistance. This thesis investigates the development, characterisation, and evaluation of the radiation performance of AlFeMnNiCux HEAs, focusing on their potential utilisation as structural materials in Gen-IV nuclear reactors and other extreme environments, such as fusion reactors and space exploration. This thesis studies the effects of Cu as a minor element on the mechanical properties and microstructural evolution of HEAs under irradiation. Vacuum arc melting (VAM) was used to synthesise a series of AlFeMnNiCux alloys with different Cu content (x = 0, 0.05, 0.1, 0.25, 0.5 and 1) and these HEAs were characterised using advanced methods such as scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The results showed that the addition of Cu caused the formation of nanoprecipitates, which significantly enhanced alloy hardness and radiation tolerance. Optimal Cu content where this nanoprecipitation is achieved, was determined to be 2 at.% to give well defined and uniformly distributed face centred cubic (FCC) nanoprecipitates in a body centred cubic (BCC) matrix. HEAs were irradiated with low-energy (6 keV He) ion irradiation to simulate fission product implantation to study helium bubble formation and growth and medium-energy (300 keV Ar) ion irradiation to simulate neutron damage. Real-time damage evolution examinations were also performed using in situ TEM irradiation experiments at the MIAMI-2 facility, which provided insights into the mechanisms of defect formation and growth in HEAs during exposure to radiation across a broad range of dosages and temperature conditions relevant to nuclear applications. The results showed that the addition of nanoprecipitates to AlFeMnNiCu0.1 increased radiation tolerance, as helium bubble formation was delayed and growth slowed, suggesting that the nanoprecipitates acted as efficient defect and/or gas atom sinks. The effects of temperature on radiation-induced damage were also investigated in this thesis, in which irradiation was performed at room temperature, 350 °C, and 500 °C. The AlFeMnNiCux HEA system offers the opportunity to xv design materials with specific thermal stability and room-temperature performance characteristics by controlling their microstructure and composition. These findings underscore the importance of fabricating alloys and their microstructures from composition to a set of conditions. This thesis concluded that engineered HEAs may enable extreme environmental applications. The addition of Cu enhances the mechanical properties and radiation tolerance owing to the formation of nanoprecipitates. However, the complex interplay between the composition, microstructure, temperature, and radiation effects necessitates careful optimisation for specific applications. These findings contribute to the broader field of materials science and provide a foundation for future research on advanced alloys for nuclear and space applications. Future work should focus on developing economically feasible HEAs with elements suitable for nuclear applications, ensuring long-term stability under extreme conditions, and exploring their use as coatings for accident-tolerant fuel claddings and nuclear waste storage.