Maternal substance use has often been associated with insecure and disorganized child attachment. We evaluated this association with a meta-analysis of young children and, further, systematically reviewed mediating and moderating factors between maternal substance use and child attachment. We performed a systematic database search of quantitative English language studies on child attachment that included substance-using mothers and their children below 6 years of age. Eleven studies (N = 1,841) met the inclusion criteria and were included in the meta-analysis of attachment security and seven (N = 1,589) studies were included in the meta-analysis of attachment disorganization. We found that maternal substance use was negatively associated with secure attachment in children, but the effect size was small (r = −.10). The association with disorganized attachment was not significant (r = .15). Related to moderating and mediating factors (k = 6), we found evidence on the role of teratogenic and sociological factors on child attachment. Most importantly, the impact of cumulative risks was vital. However, literature was scarce, and studies varied in risk of bias, leaving many unanswered questions on other potential factors underlying the development of attachment in these high-risk children. We discuss the results considering clinical implications and future directions.