Rapid urbanization, industrialization, and agricultural intensification have resulted in serious soil problems, such as soil acidification and cadmium pollution, affecting food security and human health. Wheat is the second largest food crop in China and has a strong accumulation capacity for cadmium. Understanding the influencing factors of cadmium content in wheat grain is crucial to realize the safe production of wheat. However, a comprehensive and quantitative analysis of how soil physicochemical properties and cultivars affect wheat cadmium accumulation is lacking. The Meta-analysis and decision tree analysis of 56 related studies published in the past 10 years showed that the proportion of cadmium content in soil and wheat grain exceeding the national standard was 52.6% and 64.1%, respectively. Among soil physical and chemical properties, pH, organic matter, available phosphorus, and total soil cadmium content were the important factors affecting the cadmium content in wheat grains. When soil pH ≤ 5.5 and 5.5<pH ≤ 6.5, the proportion of cadmium content in wheat grain exceeding the national standard was 99.4% and 76.2%, respectively. When 20 g·kg-1<soil organic matter content ≤ 30 g·kg-1, the proportion of cadmium content in wheat grain exceeding the national standard was the highest (61.0%). Soil pH ≥ 7.1 and total cadmium content <1.60 mg·kg-1 was suitable for wheat safety production. There were significant differences in grain cadmium content and cadmium enrichment factors among different wheat cultivars. Planting wheat cultivars with low cadmium accumulation is an economical and effective measure to decrease cadmium content in wheat grains. The current study can provide guidance for the safe production of wheat in cadmium-contaminated farmland.