The purpose of this systematic review is to assess evidence for an association between opioid misuse and suicide-related outcomes among youth and young adults (aged 12-30 years). A Boolean search strategy of eligible publications from January 1990 to June 2024 identified 2,696 independent citations. An additional 10 were identified through reference screening. A total of 55 publications met the inclusion criteria. Twelve studies used administrative data and 43 were based on observational data. Risk of bias was assessed qualitatively by domain. Nearly all (98%) studies using observational data found an association between opioid misuse and at least one suicide-related outcome (e.g., suicidal ideation, suicide plan, suicide attempt). Administrative data studies had higher risk of bias compared with observational studies, typically due to higher confounding bias. Reporting bias was moderate to high across all studies in the review. Our review provides clear evidence of the association between opioid misuse and suicide-related outcomes among youth and young adults. However, we highlight a need for longitudinal research on the directionality of the association and potential mechanisms.