Icosahedral boron clusters have gained increasing attention as biomedical platforms for integrated imaging and therapy. Their outstanding chemical and metabolic stability, high boron density, and structural adaptability enable the design of multifunctional agents that combine diagnosis and treatment within a single molecular or nanoscale construct. This chapter focuses on the biomedical exploitation of boron cluster-based systems for cellular bioimaging and in vivo theranostics, with particular emphasis on boron neutron capture therapy (BNCT). At the in vitro level, boron clusters have been incorporated into fluorescent probes and photoactive conjugates to investigate structure-property-activity relationships, cellular uptake, organelle targeting, and photodamage and illustrate how subcellular localization controls combined BNCT and photodynamic efficacy. In vivo, Gd-carborane systems exemplify MRI-guided BNCT and GdNCT, evolving from LDL-based nanoplatforms to CAIX-targeted small molecules that couple image-based dosimetry with dual neutron capture at the tumour site. Complementary PET/SPECT-radiolabelled boron clusters and nanocarriers enable quantitative tracking of boron biodistribution, patient selection, and irradiation timing. Furthermore, targeted and nanostructured formulations improve tumour selectivity and therapeutic efficacy while reducing off-target toxicity. This chapter highlights how icosahedral boron clusters have evolved into clinically relevant theranostic platforms that integrate imaging, dosimetry, and therapy, supporting the development of more precise and personalized strategies in cancer diagnosis and treatment.