Nitrogen fertilizer is the most frequently used fertilizer in the cultivation of medicinal plants, and has a significant contribution to their yields and quality. Yet, there is biased and excessive N application in medicinal crops. This study aims to quantitatively analyze the recommended N application concentrations for diverse medicinal species and disentangle the intricate relationships between soil fertility, N application rate (NAR), and the quality/yield of medicinal crops. We first characterized 179 medicinal species and 7 classes of phytometabolites therein, including terpenoids, flavonoids, phenylpropanoids, phenolics, alkaloids, etc., reported during the past three decades from the phylogenetic and spatial perspectives. The relationships between soil fertility, NAR, and medicinal crops were then subjected to statistical analyses. The pharmaco-phylogenetic and geographic distributions of NAR suggest that the impact of ecological/environmental factors on the N demand of medicinal plants was much greater than that of genetic endowments. We found that different medicinal species were distinct in N demand, which is related to soil fertility levels in different production areas. The NAR reported by China, 215.6 ± 18.6 kg/ha, was higher than that of other countries (152.2 ± 20.3 kg/ha; p = 0.023). Moderate N application generally increases the yield and phytometabolite content of medicinal crops, but excessive N application has the opposite effect. It is necessary to plan N concentration and formula fertilization on a case-by-case basis and with reference to empirical research. Our results provide baseline information and references for the rational application of N fertilizer in the precision agriculture of medicinal crops.