Objectives: To investigate the prevalence and associated factors of drug abuse among the Saudi population. Methods: To locate relevant material, we searched PubMed, SCOPUS, Web of Science, and Science Direct thoroughly. The Rayyan QRCI was used during the procedure. Results: We included six studies with a total of 33222 patients, and 20,803 (62.6%) were males. Drug abuse prevalence ranged from 2.4% to 58.8%. The most common drugs used were amphetamine-cannabis benzodiazepine, Amphetamines & cannabis, Stimulants & cannabis, Heroin & alcohol, Khat chewing, and Marijuna & narcotic drugs. Patients' age, smoking habits, past medical history, and age at the beginning of drug use, male gender unmarried people, and Saudi nationals, used drugs at substantially greater rates. Interestingly, participants with higher education levels were more likely to use drugs such as amphetamines and cannabis while lower educational attainment were more likely to use Khat. Conclusion: When it came to substance misuse, the general Saudi population that visited health facilities had a pretty high rate. In light of these findings, we recommend carrying out additional research to obtain more precise and pertinent information about the incidence of substance usage in Saudi Arabia. To determine the incidence of morphine abuse across various populations, including healthcare professionals and people with chronic pain—such as sickle cell patients—we advised conducting additional research.