Objectives: The current study aims to perform a cluster analysis on heart knowledge and risk perception of substance misusers and their correlates. Methods: In this cross-sectional study, 156 participants (96.2% male, 18-65 years old with M ± SD = 39.0 ± 11.9) were selected using stratified random sampling. Heart disease knowledge questionnaire (HDKQ) and perception of risk of heart disease scale (PRHDS) were the data gathering tools. The findings were analyzed using two-step cluster analysis and multinomial logistic regression analysis. Results: This model suggested three clusters: (i) moderate knowledge with good risk perception (32.7%), (ii) moderate knowledge with poor-risk perception (44.9%), and (iii) poor knowledge with low cardiac risk perception (22.4%). Single individuals (P = 0.044, P = 0.014) and participants without a family history of hypertension (P = 0.045) show lower heart knowledge and risk perception. This model was able to accurately predict 20.3% to 39.8% of the variance in the criterion variable. Conclusions: Cluster analyses can appropriately partition substance misusers based on their level of heart knowledge and cardiac risk perception. The identified vulnerable groups are affected by a number of demographics and family histories of chronic diseases. The results of the current study provide useful insights for family physicians and cardiovascular health professionals.