Neuroscience offers the tantalizing future prospect of personalized precision medicine for brain disorders. Non-invasive brain stimulation has distinctive therapeutic promise. It offers potential means to reshape brain function into adaptive states. On the road to unlock this promise, one key challenge is variability. Individuals differ – in their physiology, behaviour, and in response to stimulation. The factors that determine this variability are not understood. I will outline how we have begun to address this over the last decade in our work. I will present a causal mechanistic account of individual variation in response to a plasticity protocol with therapeutic benefits in chronic stroke. By using computational modelling we could identify structural, functional and neurochemical bases of individual differences in behaviour and in response to stimulation-induced behaviour change. Understanding the neural bases of phenotypic variation and its modifiability by intervention is an essential step on the path towards personalized brain stimulation therapies.