The phenomenon of touristification—the transformation of urban spaces driven by tourism—has increasingly shaped the socio-economic and spatial dynamics of many cities worldwide. This paper presents a comprehensive framework for assessing touristification at the neighbourhood level, with a particular focus on Naples, Italy. Leveraging a Spatial Decision Support System (SDSS), the study integrates both prescriptive and descriptive models to evaluate tourism’s impact on local real estate, short-term rentals and socio-economic status. Key challenges such as the geometric misalignment of mapping units, criteria selection for indicators and data availability are addressed, highlighting invariant factors, conceived as operational opportunities and constraints, to structure a SDSS capable of capturing the complexity of tourism-driven urban transformations. By bridging this gap, this study provides actionable recommendations for policy-makers to manage tourism-related pressures, protect residential accessibility and promote sustainable urban development.