In this study, novel non-equiatomic CoCrFeMnNi-based medium- and high-entropy alloys (M/HEAs) were designed to activate distinct deformation mechanisms, including twinning-induced plasticity (TWIP) and/or transformation-induced plasticity (TRIP). Tensile tests were performed at 298 and 173 K. A variety of ex-situ multiscale characterization techniques, strengthening modeling, thermodynamic modeling (CALPHAD method), and ab initio density functional theory (DFT) calculations were employed to investigate the structural and microstructural evolution, enabling accurate identification of the strengthening and active deformation mechanisms operating in the M/HEAs. Strengthening modeling revealed that grain boundary strengthening was the primary contributor to yield strength at both temperatures. A key finding of this study is that a controlled FCC→HCP martensitic transformation, associated with TRIP, enhances the strength-ductility balance even when the resulting HCP phase reaches ∼50% volume fraction. This demonstrates that TRIP-enabled metastability engineering is a promising strategy for designing high-performance M/HEAs for next-generation structural applications in energy, aerospace, and defense.