Background: Dilated cardiomyopathy (DCM) is one of the most common types of cardiomyopathies. The current study constructs a proposed genetic risk score and assesses its potential as a predictive tool for individual DCM susceptibility. Methods: A total of 1,000 patients with idiopathic DCM and 828 control participants from the study institution were enrolled. The top 25 up-regulated and down-regulated genes from tandem mass spectrometry analysis of 6 hearts with DCM and 7 control hearts (from a study by Chen et al) were selected for logistic analysis using whole-exome sequencing data. Statistically significant variants were prepared for genetic risk score construction. The predictive power of the genetic risk score and a composite variable for DCM risk were evaluated using receiver operating characteristic curve analysis. Results: A total of 5 variants associated with DCM susceptibility were identified to develop the genetic risk score. A score of at least 6.4 was more strongly associated with increased risk of DCM (odds ratio, 2.4; P < .001) than scores lower than 6.4. Statistical significance remained evident in multivariate analysis after adjusting for traditional risk factors, including age, sex, hypertension, diabetes, and smoking status (odds ratio, 2.54; P < .001). Individuals with a score of at least 6.4 exhibited a decrease in left ventricular ejection fraction and an increase in left ventricular end-diastolic diameter compared with individuals with a score lower than 6.4 (P < .001). Stratification by age, sex, history of hypertension, diabetes, and smoking status did not substantially affect the association between genetic risk score and the risk of DCM. The discriminant power of the genetic risk score is excellent, with a C statistic of 0.72. Conclusion: The genetic risk score, which consists of 5 variants, could effectively identify individuals at high risk of DCM in the study population and aid in the implementation of early prevention strategies in clinical practice.