Experiences of complex trauma and adversity, especially for children, are ongoing global crises necessitating adaptation. Bioadaptability to adversity and its health consequences emphasizes the dynamism of adaptation to trauma and the potential for research to inform intervention strategies. Epigenetic variability, particularly DNA methylation, associates with chronic adversity while allowing for resilience and adaptability. Epigenetics, including age- and site-specific changes in DNA methylation, gene-environment interactions, pharmacological responses, and biomarker characterization and evaluation, may aid in understanding trauma responses and promoting well-being by facilitating psychological and biological adaptation. Understanding these molecular processes provides a foundation for a biologically adaptive framework to shift public health strategies from restorative to long-term adaptation and resilience. Psychological, cultural, and biological trauma must be addressed in innovative interventions for vulnerable populations, particularly children and adolescents. Understanding molecular changes may provide a biopsychosocial perspective for culturally sensitive, evidence-based interventions that promote resilience and thriving in new settings.