Virtual reality (VR) represents a key technology of the 21st century, attracting substantial interest from a wide range of scientific disciplines. With regard to clinical neuropsychology, a multitude of new VR applications are being developed to overcome the limitations of classical paradigms. Consequently, researchers increasingly face the challenge of systematically evaluating the characteristics and quality of VR applications to design the optimal paradigm for their specific research question and study population. However, the multifaceted character of contemporary VR is not adequately captured by the traditional quality criteria (ie, objectivity, reliability, validity), highlighting the need for an extended paradigm evaluation framework. To address this gap, we propose a multidimensional evaluation framework for VR applications in clinical neuropsychology, summarized as an easy-to-use checklist (VR-Check). This framework rests on 10 main evaluation dimensions encompassing cognitive domain specificity, ecological relevance, technical feasibility, user feasibility, user motivation, task adaptability, performance quantification, immersive capacities, training feasibility, and predictable pitfalls. We show how VR-Check enables systematic and comparative paradigm optimization by illustrating its application in an exemplary research project on the assessment of spatial cognition and executive functions with immersive VR. This application furthermore demonstrates how the framework allows researchers to identify across-domain trade-offs, makes deliberate design decisions explicit, and optimizes the allocation of study resources. Complementing recent approaches to standardize clinical VR studies, the VR-Check framework enables systematic and project-specific paradigm optimization for behavioral and cognitive research in neuropsychology.