The need for 24/7 operation, and the increasing requests of high-quality healthcare services contribute to framing healthcare facilities as a complex topic, also due to the changing and challenging environment and huge impact on the community. Due to its complexity, it is difficult to properly estimate the construction cost in a preliminary phase where easy-to-use parameters are often necessary. Therefore, this paper aims to provide an overview of the issue with reference to the Italian context and proposes an estimation framework for analyzing hospital facilities’ construction cost. First, contributions from literature reviews and 14 case studies were analyzed to identify specific cost components. Then, a questionnaire was administered to construction companies and experts in the field to obtain data coming from practical and real cases. The results obtained from all of the contributions are an overview of the construction cost components. Starting from the data collected and analyzed, a preliminary estimation tool is proposed to identify the minimum and maximum variation in the cost when programming the construction of a hospital, starting from the feasibility phase or the early design stage. The framework involves different factors, such as the number of beds, complexity, typology, localization, technology degree and the type of maintenance and management techniques. This study explores the several elements that compose the cost of a hospital facility and highlights future developments including maintenance and management costs during hospital facilities’ lifecycle.