Considerable evidence is emerging that Autism Spectrum Disorder (ASD) is most often triggered by a range of different genetic variants that interact with environmental factors such as exposures to toxicants and changes to the food supply. Up to 80% of genetic variations that contribute to ASD found to date are neither extremely rare nor classified as pathogenic. Rather, they are less common single nucleotide polymorphisms (SNPs), found in 1–15% or more of the population, that by themselves are not disease-causing. These genomic variants contribute to ASD by interacting with each other, along with nutritional and environmental factors. Examples of pathways affected or triggered include those related to brain inflammation, mitochondrial dysfunction, neuronal connectivity, synapse formation, impaired detoxification, methylation, and neurotransmitter-related effects. This article presents information on four case study patients that are part of a larger ongoing pilot study. A genomic clinical decision support (CDS) tool that specifically focuses on variants and pathways that have been associated with neurodevelopmental disorders was used in this pilot study to help develop a targeted, personalized prevention and intervention strategy for each child. In addition to an individual’s genetic makeup, each patient’s personal history, diet, and environmental factors were considered. The CDS tool also looked at genomic SNPs associated with secondary comorbid ASD conditions including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections/pediatric acute-onset neuropsychiatric syndrome (PANDAS/PANS). The interpreted genomics tool helped the treating clinician identify and develop personalized, genomically targeted treatment plans. Utilization of this treatment approach was associated with significant improvements in socialization and verbal skills, academic milestones and intelligence quotient (IQ), and overall increased ability to function in these children, as measured by autism treatment evaluation checklist (ATEC) scores and parent interviews.