Autism spectrum disorder (ASD) and intellectual disability (ID) are severe neurodevelopmental conditions with early childhood onset and considerable clinical overlap. Able to be diagnosed at birth and with high penetrance of both ASD and ID, Tuberous Sclerosis Complex (TSC) provides unique opportunity for characterizing the earliest stages of ASD with and without coexisting ID. A comprehensive strategy spanning preclinical and clinical studies is being pursued in TSC to develop imaging and electrophysiologic biomarkers that predict ASD/ID risk and gain insight into the underlying structural and functional changes associated with the earliest stages of ASD and ID. The learning objectives of this panel are to (1) understand the phenotypic features of ASD and ID in TSC throughout the lifespan; (2) appreciate the challenges in ASD and ID assessment and treatment (including both pharmacologic and non-pharmacologic interventions) at young ages in high-risk populations such as TSC; and (3) review the latest progress in both animal models and human studies of TSC to develop imaging and electrophysiologic biomarkers that predict disease risk and assess treatment response in early ASD and ID.