Ti14.286Al14.286Cr14.286Nb14.286Ni14.286Cu14.286Co14.286 (A), Ti20Al20Cr5Nb5Ni19Cu12Co19 (B), Ti20Al20Cr5Nb5Ni18Cu14Co18 (C) and Ti20Al20Cr5Nb5Ni17Cu16Co17 (D) optimized high entropy alloys (HEAs) were designed theoretically by thermo-physical calculations and CALPHAD-based tool (ThermoCalc) to predict the thermodynamic and mechanical properties of the alloys prior to the experimentation process. After wet mechanical alloying of the elemental powders at 10 hrs milling time, the pulse electric sintering technique was utilized in the fabrication of the HEAs at a sintering temperature of 900 oC, heating rate of 100 oC/min, pressure of 50 MPa, and a dwelling time of 5 min. X-ray diffractometer, scanning electron microscope, and nanoindentation testing were used to investigate the distinct phase constituents, microstructures and nano-mechanical characteristics of the fabricated HEAs. While principally 5 stable phases (BCC_B2, FCC_L12, Sigma, Heusler and C15_Laves) were present at varying fractions for all four HEAs, simulation from the Property Model Calculator (PMC) module of the ThermoCalc software reveals the intrinsic hardness of 126.116 HV, 144.096 HV, 138.283 HV and 132.972 HV for alloys A, B, C and D respectively. At 100 mN load, 600 mN/min loading and unloading rate, and 2 secs holding period, a corresponding result obtained from the nanoindentation technique confirms alloy B exhibits the highest nanohardness (15.185 GPa), with the least penetration depth (427.822 nm) and highest elastic modulus (246.92 GPa) among other properties. From observation, an increase in the composition of the Cu at the expense of Ni and Co results in the BCC-FCC phase transformation, and this translates to an obvious decrease in the nanohardness value from alloy B to D. A comparison of the hardness results simulated from the PMC module of the ThermoCalc software, and the nano-hardness results obtained experimentally from the nanoindentation technique parades a similar trend.