BACKGROUND: Prenatal stress is known to disrupt neurodevelopment in offspring, heightening their risk of mental health disorders. However, its impact on the morphometric similarity network (MSN)-a framework that integrates multiple anatomical features to quantify structural similarity across brain regions in the developing offspring-remains poorly understood. METHODS: Using data from the Queensland Twin Adolescent Brain (QTAB) longitudinal study focusing on adolescent twins, we investigated the impact of prenatal stress on cortical MSN in 414 early adolescents (aged 9-14 years). Furthermore, we analyzed the relationship between MSN strength alterations associated with prenatal stress and anatomically organized gene expressions. Disease-related analysis and functional enrichment analysis were conducted. RESULTS: Adolescents exposed to prenatal stress exhibited smaller age-related changes in MSN strength between ages 9 and 14, particularly in regions associated with emotional regulation, cognitive control, and decision-making, despite showing greater similarity at age 9 compared to their unexposed peers. We identified cortical patterns characterized by weighted gene expression, strongly associated with group differences in MSN strength. Gene expressions linked to prenatal stress-related MSN strength changes were correlated with differential gene expression (DGE) implicated in conditions such as autism spectrum disorder (ASD) and inflammatory bowel disease (IBD). CONCLUSIONS: These results enhance insights into the interplay between gene expression and structural brain changes driven by prenatal stress, highlighting a potential mechanistic link between prenatal stress and neurodevelopmental vulnerability, shedding light on the biological pathways underpinning neurodevelopmental risk factors.