Attention-Deficit Hyperactivity Disorder (ADHD) and Post-Traumatic Stress Disorder (PTSD) are prevalent psychiatric conditions often occurring concurrently. Existing research has studied these disorders independently, but have largely overlooked their substantial genetic overlap. Consequently, our study takes a novel approach, partitioning data into three distinct sets, focusing on the shared components, thereby increasing statistical power. As there is a need for improved targeted and effective treatments, and enhanced understanding of the biological mechanisms underlying the aetiology of both disorders, this study investigates the genetic factors that link ADHD and PTSD by identifying the shared genetic factors and biological mechanisms that potentially underlie both disorders. This project employs an integrative approach, combining genomic analyses, gene-level analyses, transcriptome-wide association studies, colocalization analyses, gene-set enrichment analyses and drug-gene association analyses on partitioned summary statistics representing unique genetic effects for ADHD and PTSD, respectively, and genetic effects shared between ADHD and PTSD. We identified 19 shared genomic risk loci, suggesting common genetic architecture. Additionally, our gene-level analysis identified 34 genes that reached genome-wide significance (23 novel), while our TWAS analysis unveiled 47 gene-trait associations (39 novel), all in pathways critical for neural communication, synaptic plasticity, and stress response, providing potential therapeutic targets. Moreover, genetic factors contributing to ADHD and PTSD were revealed, with findings that may provide insights into the genetic and biological mechanisms of both disorders and identify potential drug targets for future research.