In the era of "big data", we are gaining rich person-specific information about neuroanatomy, neural function, and cognitive functions. However, the optimal ways to create precise approaches to optimize individuals' mental functions in health and disease are unclear. Multimodal analysis and modeling approaches can guide neuromodulation by combining anatomical networks, functional signal analysis, and cognitive neuroscience paradigms in single subjects. Our progress could be improved by progressing from statistical fits to mechanistic models. Using transcranial magnetic stimulation as an example, we discuss how integrating methods with a focus on mechanisms could improve our predictions TMS effects within individuals, refine our models of health and disease, and improve our treatments.