Research on the application of high-Z nanoparticles (NPs) in cancer treatment and diagnosis has recently been the subject of growing interest, with much promise being shown with regards to a potential transition into clinical practice. In spite of numerous publications related to the development and application of nanoparticles for use with ionizing radiation, the literature is lacking coherent and systematic experimental approaches to fully evaluate the radiobiological effectiveness of NPs, validate mechanistic models and allow direct comparison of the studies undertaken by various research groups. The lack of standards and established methodology is commonly recognised as a major obstacle for the transition of innovative research ideas into clinical practice. This review provides a comprehensive overview of radiobiological techniques and quantification methods used in in vitro studies on high-Z nanoparticles and aims to provide recommendations for future standardization for NP-mediated radiation research.