Medium carbon steels alloyed with two levels each of V and Si were heat treated to form tempered martensite and bainite, followed by nitriding to evaluate their effects on case hardness and residual stress. Microstructures were quantitatively characterized with Vickers microhardness testing, scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), X-ray diffraction (XRD), conventional transmission electron microscopy (CTEM), and scanning transmission electron microscopy (STEM). Measurements of subgrain size, cementite size, dislocation density, and volume fractions of nitride precipitates were combined in a strength model to predict the contributions of V and Si to maximum case hardness after nitriding. Higher V contents lead to increases in maximum case hardness by increasing the volume fraction of MX precipitates. Increases in Si content lead to increased maximum case hardness by increasing the volume fraction of amorphous (Si and Mn)-containing nitride precipitates; the presence of Mn in these precipitates has not been previously reported. Higher Si contents also lead to increases in solid solution strengthening because the majority of Si remains in solution in the ferrite matrix. Greater volume fractions of MX and (Si and Mn)-containing nitrides both lead to higher magnitudes of compressive residual stress. The results presented here demonstrate that alloying can improve the properties after nitriding, providing insight into advanced nitriding steel grades and potentially enabling a wider range of steel microstructures to be nitrided without a debit in performance.