Since the industrial revolution, the relationship between unemployment and psychiatric disorders has been a subject of high interest. Currently, regarding the correlation between unemployment and substance-use disorders (SUDs), only older, often isolated and fragmented research results are available in the literature. This review was based on an extensive literature search of the European and North American literature in most relevant databases for "unemployment" and "substance use" related to "drugs", "alcohol", "nicotine", and "tobacco" between November 2022 and January 2023, according to the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) guidelines. A total of 59,117 papers were identified, of which only 33 articles were identified as relevant to the research objective. The literature showed significantly higher prevalence rates of SUDs involving divergent psychotropic substances among unemployed people. Unemployment was found to be a risk factor for SUD, and vice versa. However, the correlation between unemployment and relapses or smoking cessation was inconsistent. In addition, there appeared to be a mild effect of business cycles on SUD. The results showed significant multifaceted correlations between unemployment and SUD, indicating that prevention and early intervention are required to prevent harmful psychosocial consequences, such as social disintegration and severe psychiatric disorders.