Background: Substance use disorder is a Chronic relapsing brain disease characterized by a psychological and physical dependence on either substance like drugs or alcohol, and leads to significant impairment or tolerance, and withdrawal symptoms. It also applies to behaviors like gambling or video gaming. This study aims to provide an overview of substance use disorder among Jerusalem and Palestinian Citizens in Israel patients. Study Methodology: A case-control study was conducted among 956 Patients admitted to the Palestinian National Rehabilitation Center from January 2021 to August 2024. We extracted all data: gender, age, marital status, duration of adduction, and type of substance abuse. Results: The mean age of patients was 31 years old, (97.2%) of participants were male, 16.4% had completed university education, the mean duration of substance use was 13 years, and (34.7%) of patients were using for more than 16 years, (64.0%) of patient used cannabis, (21.0%) opioids, (18.9%) alcohol, (5.1%) cocaine. The multivariate analysis showed that the Jerusalem and Palestinian citizens of Israel patients were 1.32 times more likely to have a longer duration of substance use compared to the West Bank. Conclusion: This is the first study that examines the relation between Substance use and place of residency in Palestine; Most of the study results are compatible with international studies with differences in numbers and percentage. However, investigating substance use among Jerusalem and Palestinian citizens in Israel requires an understanding of many factors including social, and economic conditions, the influencing of culture, and the effect of the political environment to improve prevention, treatment, and rehabilitation strategies in Palestine.