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Substance use problems among the homeless population represents a major issue leading to increased morbidity and mortality. The aim of this review was to investigate the prevalence, trends and effects of substance use among the homeless population. Studies were identified through electronic searches of Google Scholar, Science Direct, Medline, Embase and Scopus between January 2007 and December 2020. Studies included were those reporting substance use and homelessness within the age range of 18–64 years old, whereas interventional and rehabilitation studies were excluded. Subsequently the extraction yielded twenty-five studies. The results showed that substance use was more prevalent in males than females and alcohol the most popular substance used among the homeless population. After 2017, however, both alcohol and new psychoactive substances (NPS) were equally a problem. This urges the need to develop research in homelessness and NPS consumption to increase awareness among health care providers, governmental agencies and academics.