The invention of concentrated solid solution alloys (CSAs) has vastly expanded the compositional space of alloys, which provides properties that cannot be achieved by conventional alloys. Ni-based CSAs have shown the potential for exceptional toughness and radiation resistance, which make these alloys viable candidate materials for energy and nuclear industries. Different from conventional alloys with only one principal element, CSAs contain multiple elements with equal or near equal compositions and have unique intrinsic properties such as a high entropy effect, severe lattice distortion, sluggish diffusion, and cocktail effect. However, as new-emerging materials, the theoretical and experimental investigations on their performances are still limited. The goal of this thesis is to (a) develop nanomechanical methods to exact mechanical properties of Ni-based CSAs. (b) apply nanomechanical methods to detect radiation-induced defects and radiation hardening of Ni-based CSAs. (c) yield stress-strain curves directly from flat punch nanoindentation to study the effect of radiation on work hardening behaviors of Ni-based CSAs.First, we explore the deformation mechanisms of a set of five Ni-based CSAs, including NiCo, NiFe, Ni80Cr20, N80Mn20, and NiCoFeCr, by nanoindentation with the Berkovich tip. We developed a complete methodology for nanoindentation to extract accurate hardness, elastic modulus and strain rate sensitivity and investigate deformation mechanisms, considering indentation size effect. Our results show that the most effective strengthening mechanisms in these alloys are attributed to lattice distortion from the mismatch in atomic size. The element type of alloying elements plays a more important role than the number of alloying elements in strengthening CSAs. Second, based on the first study above, nanoindentation is further used to study the early-stage radiation-induced damage on NiCo, NiFe and NiCoFeCr. Understanding the defect nucleation and accumulation at the nascent stage is important but challenging due to the difficulty of quantifying point defects induced by low-dose irradiation at this regime. It is hypothesized that the interactions between radiation-induced defects and deformation-induced dislocations can be used to quantify the radiation-induced defects. The distinct radiation-induced hardening observed in three CSAs can be explained by two factors: the formation of radiation-induced defects and the increased density of geometrically necessary dislocations (GNDs) related to the indentation size effect (ISE). Quantitative analysis reveals significant hardening caused by radiation-induced defects in NiFe and NiCoFeCr sample, but not in the NiCo sample. Meanwhile, the irradiation results in a higher GND density in NiCo and NiFe, but not in NiCoFeCr, which is attributed to the volume change of the plastic zone. Lastly, conventional nanoindentation cannot produce data that can be converted into a uniaxial stress-strain curve for easy evaluation of materials properties. Therefore, in the final part, we strive to achieve uniaxial stress-strain curves of unirradiated and irradiated CSAs by 1-µm flat punch indentation. The protocol is developed based on Hay’s method with consideration of thermal drift and successfully capture strength and work hardening of CSAs. The radiation hardening is pronounced in both NiCo and NiCoFeCr, though NiCoFeCr exhibits less hardening and a lower dependency on radiation dose. In addition, strain hardening capability degrades due to irradiation in both NiCo and NiCoFeCr with the degradation being less obvious in NiCoFeCr. This suggests that flat punch nanoindentation could be a promising tool for understanding radiation-induced property degradation and accelerating the development of new alloys.