Swift ions in matter exhibit favorable physical and biological properties, particularly owing to the ability of concentrating their energy deposition at a well-localized depth at their end of range, so-called Bragg peak. However, despite considerable recent technological advances, particularly regarding ion accelerators and scanning beam delivery systems, along with integration of in-room volumetric X-ray imaging, full clinical exploitation of the favorable ballistic properties of ion beams is still hampered by the yet unsolved problem of range uncertainties, preventing exact localization of the Bragg peak in tissue. Although these uncertainties can be mitigated by the introduction of cautious safety margins and careful choice of beam directions, new approaches are being extensively investigated to tackle this issue at the stage of treatment planning and treatment delivery. Here, emphasis will be given to pre-treatment transmission imaging of multi-energy X-ray sources or energetic ion beams for refined assessment of the tissue stopping properties pre-treatment, along with online/post-treatment detection of acoustic and nuclear-based emissions induced by ion interaction in tissue for in vivo verification of the beam range. Also, ongoing activities toward precision small animal radiation research at conventional and laser-driven sources will be briefly outlined.