Many studies have revealed that individuals who engage in simultaneous use of alcohol and cannabis report elevated substance‐related consequences relative to those who use only alcohol or cannabis; however, evidence from emerging studies examining within‐person differences across simultaneous use and single substance use occasions is less consistent. This systematic review aimed to synthesize findings from existing day‐ and event‐level studies of within‐person differences in the proximal antecedents and acute outcomes associated with simultaneous use versus single substance use episodes. Our search strategy revealed 30 eligible articles. Two categories of antecedents (i.e., internal [e.g., motives] and external [e.g., social context]) and three categories of outcomes (i.e., consumption behavior, general positive and negative consequences, and specific consequences) were identified. The current literature consistently suggests that greater day‐ or event‐level social and enhancement motives, as well as being in a social context, predict greater likelihood of engaging in simultaneous use compared with alcohol‐ or cannabis‐only use. However, there was heterogeneity in findings regarding the role of other person‐level antecedents. Further, while most evidence pointed to heavier alcohol consumption on simultaneous use occasions versus alcohol‐only occasions, findings for elevations in acute negative and positive substance‐related consequences on simultaneous use versus single substance use occasions were mixed. Additionally, four studies found that increased consequences on simultaneous use occasions depended on the level of alcohol consumed. This review identifies several antecedents for simultaneous use events but suggests that simultaneous use occasions are not always associated with more acute harms than single substance use occasions. Given the extent to which the current literature is mixed, this review emphasizes the importance of methodological improvements and future research examining the mechanisms linking simultaneous use with substance‐related consequences to help reconcile findings across within‐person and between‐person studies.