Background: Substance use is a growing public health problem among adolescents. In the lack of a valid and reliable instrument based on social development model (SDM), this study aimed to develop risk and protective factors of substance use scale based on SDM to determine risk and protective factors influencing substance use among adolescents. Methods: A total of 235 male students from 9th and 10th grade (14-18 years old) of public high schools in Kerman, Iran, selected through multistage cluster sampling. Items pool extracted from the literature and focus groups with male adolescents. Face validity of the questionnaire assessed for readability and clarity of items. Then, an expert panel evaluated the items for content validity. Consequently, construct validity of questionnaire confirmed through exploratory factor analysis (EFA). Known group validity is determined by the degree to which the instrument shows different scores between two groups of those who had an experience in drug use and those who did not have such an experience. In addition, reliability assessed via internal consistency and test-retest. Results: About 10 factor solution (containing 38 items) emerged as a result of EFA entitled adolescent’s “beliefs on hookah and alcohol,” “bonding to parents,” “family rules on substance use,” “drug resistance skills,” “adolescent’s beliefs on hard drugs,” “situational perception on hookah and alcohol,” “rules of school,” “situational perception on hard drugs,” “attachment to school,” and “perceived opportunity at school.” The first four emerged factors explained 46% of the total variance observed. Among these factors, adolescent’s beliefs on hookah and alcohol explained a more than 25.3% of the total variance. Results indicated satisfactory internal consistency (Cronbach¢s alpha ranging from 0.71 to 0.85) and intra-class correlation coefficients (ICC) (ranging from 0.48 to 0.81). Conclusion: The risk and protective factors of substance use questionnaire are the first instrument based on the SDM. The findings showed that this questionnaire is a valid and reliable instrument for assessing determinants of substance use which can be used by researchers and policymakers in preventive initiatives.