Transdiagnostic factors are considered promising in elucidating the etiological underpinnings of psychiatric comorbidities, especially in anxiety and depression. However, their symptom-centered neurobiological substrates, encompassing the genetic macro-micro-molecular brain functional landscape, remain elusive. Here, we develop edge-centric functional brain connectome-based predictive models for transdiagnostic factors of anxiety and depression symptoms (sTDF). These factors are estimated from nonlinear Gaussian topological schemes in a nationwide sample and a twin dataset. Edge-centric connectome was found to be reproducible and generalizable neural signatures for the sTDF, showing high sensitivity in neurally representing the sTDF from edge-centric similarity patterns of attention/frontoparietal networks. Such edge-centric signatures were found moderately heritable. Genetic transcriptional analyses further revealed the biological enrichment for gene expression patterns of these edge-centric connectome emerging into vessel systems and metabolism of CMRO2 for sTDF, especially for cerebellar development in late-childhood-to-young-adulthood. Our findings shed lights on the neurobiological architectures of sTDF by clarifying edge-centeric connectome-transcriptional signature.