This work fabricated CoMoNiTa3 medium-entropy alloys using the vacuum hot pressing process of powder metallurgy technology. Micron-grade cobalt (6.3 μm), molybdenum (13.2 μm), nickel (2.4 μm) and tantalum powders (25.0 μm) were combined using ball milling. The experiments utilised various hot pressing temperatures (1000, 1050, 1100, and 1150 °C) and hot pressing pressures (20, 35, and 50 MPa) to identify the optimal parameters for CoMoNiTa3 alloys, while simultaneously investigating the differences in microstructures. The experimental results reveal that the optimal hot pressing parameters of this alloy were 1100 °C at 50 MPa for 1 h. The sintering density was enhanced to 9.65 ± 0.01 g cm−3, while the hardness, transverse rupture strength, and flexural modulus reached 85.5 ± 0.1 HRA, 1370.3 ± 90.1 MPa and 168.6 ± 12.7 GPa, respectively. Moreover, the electrical conductivity was 6.53 ± 0.13 × 104 S cm−1. Furthermore, the electron probe microanalyser, electron backscatter diffraction, and transmission electron microscopy results confirmed the face-centred cubic solid solution, Ni3Ta, and μ phases of the CoMoNiTa3 structure, and no preferred grain orientation was found.