Resumen: Background/Objectives: The ability to preserve cognitive health in aging populations increasingly relies on early detection and intervention in neurodegenerative processes. Spatial memory, a fundamental cognitive ability supporting navigation, environmental awareness, and daily independence, often deteriorates in the preclinical stages of neurodegenerative diseases. However, conventional assessment tools frequently lack ecological validity and fail to capture the multifaceted nature of spatial cognition in real-world contexts. This systematic review aims to examine the application of immersive technologies, specifically Immersive Virtual Reality (VR) and Mixed Reality (MR), in the evaluation and rehabilitation of spatial memory. Methods: Following PRISMA guidelines, a total of 42 peer-reviewed studies were selected from SCOPUS, Web of Science, and PubMed databases. We included original, peer-reviewed studies that assessed spatial memory or cognition using VR/MR in adults aged ≥50 or clinical populations at neurodegenerative risk and reported quantitative data or diagnostic validity. A narrative synthesis was performed to examine the most employed immersive tools, assessing their benefits, limitations, and practical challenges. Results: Findings indicate substantial variability in diagnostic sensitivity, ecological validity, and user engagement across platforms. Nevertheless, the evidence supports the potential of immersive environments as effective tools for the early detection of spatial disorientation and cognitive decline, particularly in at-risk populations such as individuals with Mild Cognitive Impairment and Alzheimer’s Disease. Conclusions: Immersive and semi-immersive VR technologies represent a promising advancement in spatial memory assessment and rehabilitation, offering scalable solutions for both clinical and home-based interventions in aging populations. Idioma: Inglés DOI: 10.3390/biomedicines13092105 Año: 2025 Publicado en: Biomedicines 13, 9 (2025), 2105 [30 pp.] ISSN: 2227-9059 Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2023-148731OB-I00 Financiación: info:eu-repo/grantAgreement/ES/NextGenerationEU/INVESTIGO-067-38 Tipo y forma: Artículo (Versión definitiva) Área (Departamento): Área Person.Eval.Trat.Psicoló. (Dpto. Psicología y Sociología)