Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by marked heterogeneity in biology, expression, and response to treatment. The past decade has yielded considerable progress in understanding the underlying biological mechanisms, in characterizing the earliest behavioral phenotype(s), and in developing and evaluating effective treatments for ASD. This review highlights recent research advances in genetics and neuroimaging, as well as in novel behavioral and psychopharmacological treatment approaches, arguing for the value of trans-disciplinary initiatives to move the field forward exponentially. Despite considerable complexity, patterns are beginning to emerge that can inform the identification of novel treatment targets and approaches. The next generation of major innovations in ASD research will involve collaborations across genetics/genomics, neuroimaging, and intervention science. Such efforts, currently under way, hold tremendous promise for exponentially increasing our capacity to understand the mechanisms that contribute to the emergence of ASD and to develop and evaluate personalized interventions that yield maximal impact in a meaningful way.