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Background/Objectives: The COVID-19 pandemic disrupted social structures, healthcare access, and psychological well-being, potentially intensifying substance use and suicidal behavior. Although both phenomena have been independently studied, their co-occurrence during the pandemic has not been systematically synthesized. To evaluate the prevalence and patterns of suicidal behavior among individuals with substance use during the COVID-19 pandemic through a systematic review and random-effects proportions meta-analysis. Methods: A systematic search of PubMed, Scopus, Web of Science, and EBSCO Host was conducted from 11 March 2020 to 15 October 2022 for studies published between March 2020 and October 2022. Eligible studies included observational designs reporting substance use and suicidal behavior in adults during the pandemic. Risk of bias was assessed using National Institutes of Health tools. Proportional meta-analyses were performed using a random-effects model with Freeman-Tukey double arcsine transformation. Heterogeneity was quantified using the I² statistic. Results: Twenty studies comprising 70,684 individuals were included. Substance use during the pandemic was reported in 24.6 percent of participants, while 30.7 percent exhibited suicidal behavior. A total of 16.1 percent presented with both substance use and suicidal behavior. The pooled prevalence of any suicidal behavior among individuals with substance use was 33.8 percent (95 percent CI, 22.8 to 45.7), with substantial heterogeneity. Alcohol showed a pooled prevalence of 36.2 percent, cannabis 48.1 percent, and tobacco 11.5 percent. Suicidal ideation was the most frequent outcome, with a pooled prevalence of 36.8 percent among substance users. Most studies reported an increased association between substance use and suicidal behavior compared with pre-pandemic periods. Conclusions: Substance use and suicidal behavior frequently co-occurred during the COVID-19 pandemic, particularly suicidal ideation and alcohol use. These findings highlight the need for integrated mental health and substance use interventions during public health crises.