Medicinal plant production is essential for global health, yet how temperature, precipitation, and soil properties influence yield responses to fertilization remains poorly understood. Here, we conducted a meta-analysis of 668 observations from 79 studies, focusing on a wide range of plant species, to evaluate how nutrient inputs and environmental factors interact to shape medicinal plant productivity. We found that latitude, MAT, and MAP jointly determine global medicinal plant yield patterns. Yield increased with latitude and MAT but declined under prolonged fertilization and higher MAP. Optimal cultivation regions were identified between 15 degrees and 35 degrees absolute latitude, where temperature and precipitation conditions were most favorable. Compared with the arid environment of desertic climates, other regions, especially those with higher MAP in tropical areas, show a higher increase in yield. Our findings highlight that shifting precipitation-temperature regimes under climate change will affect fertilization outcomes on medicinal plant yield, emphasizing the need for spatiotemporally adaptive nutrient management strategies to ensure the sustainable yield of medicinal plants.