Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (10B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of 10B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of 10B in a specific tissue in real-time using non-invasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. In addition, functional imaging technologies, such as PET, can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Regardless, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.