This paper aims to study the effect of hardness nitriding treatment on the overall mechanical behavior of Hardox 400 steel. A Plasma Immersion Ion Implantation (PIII) technique was used for material nitriding while a split Hopkinson pressure bar equipped with an electromagnetic heating system was used for the thermomechanical characterization of the studied steel. The collected data are analyzed to identify the combined effect of the high strain rates and elevated temperatures on the flow stress and ductility. The microstructure and the physical properties of the nitrided Hardox 400 were studied using scanning electron microscopy (SEM), X-ray diffraction, and nano-indentation tests. Although the increase of the surface hardness by 37%, the quasistatic and dynamic compression tests showed a decrease in the flow stress due to the microstructure modification caused by the increase of the temperature during the plasma nitriding process. For a better assessment of the experimental results, reduction factors for the main mechanical properties are reported. The test data from SHPB indicated a dependency of the strain rate to the temperature of untreated un-nitrided Hardox 400. Finally, a critical review of the well-known Johnson-Cook constitutive model is highlighted, where material parameters are calibrated with special attention to the thermal softening parameter. The obtained results could be of great interest for the assessment of structural components’ robustness where the combined strain rate and temperature for Hardox 400 are met.