Neurodevelopmental disorders are characterized by abnormal neural development leading to lifelong behavioral and cognitive issues. Both endogenous and exogenous factors have been shown to influence their development, and their effects have been extensively discussed. Despite this, an explanatory model does not exist. The lack of a clinically relevant framework underscores difficulties in explaining research findings as well as conundrums including heterogeneity, sex ratio differences, optimal outcome prediction, and findings such as loss of diagnosis, and onset beyond early childhood.This paper presents a model for conceptualizing the pathogenesis of neurodevelopmental disorders from the interaction of a triad of contributing factors: genetic susceptibility, cognitive compensation, and risk factors. The factors are operationalized to create a clinically relevant framework and approaches for quantification of each operationalized factor are presented. This allows clinicians to implement the framework in a practical setting, potentially improving diagnostics, and provides researchers with an explanatory framework for the conundrums mentioned above. An approach to stratification is proposed through the operationalization of risk factors. Finally, methods for testing and validation of the triad are outlined.