Background Young offspring of individuals with opioid use disorders have great exposure to a wide array of social disadvantages and stressors. This study aimed to investigate excess mortality before the age of six and predictors of premature death in children born to opioid-involved parents. Methods A total of 3210 children born between 2004 and 2009 to parents with opioid use disorders (roughly a quarter of whom were born after parental methadone treatment enrollment) were identified in Taiwan. Information concerning sociodemographic characteristics, history of medical condition, and survival status was obtained through data linkage with the National Health Insurance Database and death registration. The age-, birth year-, and sex-adjusted standardized mortality ratios (SMRs) and survival analyses were used to assess risk estimates and evaluate predictors. Results The overall SMR for children with opioid-involved parents was 2.31 (95% confidence interval [CI] = 1.68–3.10), with the estimate reaching 4.23 (95% CI = 2.37–6.97) when the causes of death were unnatural (e.g., injury and accident). The most salient predictors of premature death were low birth weight and paternal opioid problem severity, which increased risk of premature death 2.5-–5.2-fold (all P < 0.05). Being born after parents enrolled in methadone treatment was slightly associated with a reduced risk of death in those mothered by opioid users (adjusted hazard ratio = 0.30). Conclusion The elevated risk of premature death in the offspring of opioid-addicted parents suggests the need to prioritize resource allocation to safeguard this marginalized and vulnerable segment of the pediatric population.