Background <p>Evidence is limited for the association between parental income during childhood and adolescence and the subsequent risk of drug use disorder (DUD) in the second generation and whether the association is modified by region of origin. Identifying the association and effect modification by immigrant background and region of origin would provide an important knowledge base to consider tailored policies.</p> Methods <p>We used nationwide longitudinal Swedish data on 1,137,721 non-immigrants and 293,636&#xa0;s-generation individuals who turned 15 years of age between 2005 and 2020. Cox proportional hazard models were used to examine the associations between parental income and DUD by immigrant background and region of origin. Parental income was assessed in ranked percentiles based on family disposable income when the study individuals were 14 years of age. In addition, accumulated exposure and critical periods of low parental income were assessed at the ages 0–4, 5–9, and 10–14. DUD was assessed using medical/legal registers 2005–2020 when the study individuals were between 15 and 25 years old.</p> Results <p>Higher parental income was associated with a decreased risk of DUD, while the association was weaker in the second generation, such as in those from Asia, Africa, and Middle East or North Africa (MENA) in males, and Latin America or Caribbean, Africa, and MENA in females. Accumulated exposure to low parental income was associated with an increased risk of DUD, while the association was weaker in the second generation, such as in those from MENA.</p> Conclusions <p>Financial security in early life may lower the subsequent risk of DUD. However, the associations varied by immigrant background and region of origin.</p>