Decision support systems (DSSs) have been traditionally identified as useful information technology tools in a variety of fields, including the context of cultural heritage. However, to the best of our knowledge, no prior study has developed a DSS framework that incorporates all the main decision areas simultaneously in the context of cultural heritage. We fill this gap by focusing on design-science research and specifically by developing a DSS framework whose features support all the main decision areas for the sustainable management of cultural assets in a comprehensive manner. The main decision-making areas considered in our study encompass demand management, segmentation and communication, pricing, space management, and services management. For these areas, we select appropriate decision-making supporting techniques and data management solutions. The development of our framework, in the form of a web-based system, results in an architectural solution that is able to satisfy critical requirements such as ease of use and response time. We present an application of the innovative DSS framework to a museum and discuss the main managerial implications and future improvements.