Abstract: Territorial spatial functional zoning is one of the most fundamental components to shape the sustainable development–protection patterns for the high efficiency of the land and resource use. However, the conventional zoning approaches rely largely on the identification of the functional similarity or dominant land-use attributes. It is still lacking in the systematic integration of the multiple objectives, such as ecological conservation, agricultural production, and urban development. Moreover, it is very necessary to consider the cost–benefit trade-offs in the spatial zoning decisions. Especially, the effectiveness and operability of the zoning is often required in regions with intense land-use conflicts. In this study, a theoretical framework was developed for the territorial spatial functional zoning using a “goal–cost–benefit” collaborative optimization logic, according to the systematic conservation planning. The better balance coordinated the protection targets, land-use costs, and functional benefits within a unified spatial optimization. A combination of the suitability assessment, landscape pattern index analysis, and zoning optimization (Marxan with Zones) was employed to integrate the land-use survey data, NDVI-derived vegetation, point-of-interest (POI) datasets, and the socio-environmental indicators. The zoning system consisted of both dominant functional zones—including the ecological conservation, urban construction, and intensive agricultural production zones—and mixed-function zones, such as the agroforestry mixed, peri-urban agricultural, ecological recreation, and multifunctional composite zones. The hierarchical and flexible structure was represented for both single-function priorities and multifunctional land-use demands. Jiangyin City, a highly urbanized area with pronounced conflicts among ecological protection, agricultural production, and urban expansion, was selected as the empirical case in order to test the applicability of the framework. The results indicate that the optimal zoning substantially enhanced the ecological representativeness and conservation effectiveness. The protection proportions of the key ecosystem types, including the arbor forests and shrublands, increased to above 30%, indicating a significant improvement compared with the existing planning schemes. At the same time, the agricultural and urban development spaces were achieved through moderate expansion under ecological protection. The areas of the permanent prime farmland and urban development both increased, compared with the current plan. While the rise in the unit-area cost was controlled within 10%, indicating the strong overall cost-effectiveness and feasibility. The optimal zoning scheme also exhibited higher aggregation and coordination from a spatial structural perspective. The aggregation index of the intensive agricultural zone increased from 71.21 to 88.5, indicating a more compact and efficient land-use configuration. Importantly, the mixed-function zones introduced the effective transition buffers between strictly protected areas and urban construction zones, in order to avoid the potential spatial-use conflicts for the high landscape connectivity. The land-use demands were fully met to improve the resilience of the territorial spatial structure. Overall, a great contribution was also made to extend the systematic conservation planning into the territorial spatial functional zoning. The cost–benefit considerations were embedded into the zoning optimization. The empirical framework can offer practical insights to optimize the territorial spatial patterns and then refine the major function-oriented zoning, particularly in regions with high development and complex land-use conflicts.