Studies suggest that co-use of tobacco and cannabis, which is highly prevalent among cannabis users, has detrimental effects on user mental health and public health. Thus, we reviewed extant literature to determine associations between co-use of tobacco and cannabis on mental and behavioral health outcomes such as depression. We conducted a narrative literature review of manuscripts published between 2007-2022. Using two Boolean search terms, we performed a literature search across 4 databases (PubMed, Embase, PsycINFO, and Web of Science). TM reviewed the titles and abstracts for relevance to the topic. Abstracts that were not obviously relevant were discussed by the three investigators and included or excluded based on consensus. Data were extracted from the included manuscripts, including study design, population, sample size, measures of cannabis and tobacco use, and mental and behavioral health outcomes. From 19,153 literature search results across four databases, 31 articles are relevant to the narrative literature analysis. There were 15 prospective cohort studies, 7 cross-sectional studies while 9 studies included mixed methods (exploratory survey, qualitative/quantitative, longitudinal cohort). Across numerous prospective cohort and cross-sectional studies: there were consistently higher odds ratio of depression [range: 1.93 (1.27-2.93) to 3.4 (1.70-7.00)] among co-users of tobacco and cannabis compared with single or non-users. Mixed Methods studies discovered that there were higher 9-item Patient Health Questionnaire (PHQ-9) scores indicating higher severity of depression symptoms among co-users of tobacco and cannabis. Our narrative review found co-use of tobacco and cannabis is associated with increased risk of mental health disorders. While associations between cannabis and tobacco co-use and mental illness is strong, current research cannot determine whether co-use is causally related to mental illness, or whether mental illness is causally related to co-use. By understanding current trends of co-use of tobacco and cannabis research, we could develop public policy to improve public health.