Spatial decision-making is a key aspect of human behaviour. Spatial decision support systems support spatial decision-making processes by integrating required information, tools, models and technology in a user-friendly manner. While current spatial decision support systems fulfil their specific objectives, they fail to address many of the requirements for effective spatial problem solving, as they are inflexible, complex to use and often domain-specific. This research blends together several relevant disciplines to overcome the problems identified in various areas of spatial decision support. We proposed a generic spatial decision-making process and a domain-independent spatial decision support system (SDSS) framework and architecture to support the process. We also developed a flexible SDSS to demonstrate an environment in which decision makers can utilize various tools and explore different scenarios to derive a decision. The use of the system is demonstrated in a number of real scenarios across location, allocation, routing, layout, and spatio-temporal problems.