Trauma can impact individuals within a generation (intragenerational) and future generations (transgenerational) through a complex interplay of biological and environmental factors. This review explores the epigenetic mechanisms that have been correlated with the effects of trauma across generations, including DNA methylation, histone modifications, and non-coding RNAs. These mechanisms can regulate the expression of stress-related genes (such as the glucocorticoid receptor (NR3C1) and FK506 binding protein 5 (FKBP5) gene), linking trauma to biological pathways that may affect long-term stress regulation and health outcomes. Although research using model organisms has elucidated potential epigenetic mechanisms underlying the intergenerational effects of trauma, applying these findings to human populations remains challenging due to confounding variables, methodological limitations, and ethical considerations. This complexity is compounded by difficulties in establishing causality and in disentangling epigenetic influences from shared environmental factors. Emerging therapies, such as psychedelic-assisted treatments and mind–body interventions, offer promising avenues to address both the psychological and potential epigenetic aspects of trauma. However, translating these findings into effective interventions will require interdisciplinary methods and culturally sensitive approaches. Enriched environments, cultural reconnection, and psychosocial interventions have shown the potential to mitigate trauma’s impacts within and across generations. By integrating biological, social, and cultural perspectives, this review highlights the critical importance of interdisciplinary frameworks in breaking cycles of trauma, fostering resilience, and advancing comprehensive healing across generations