The integration of ecosystem processes over large spatial extents is critical to predicting whether and how global changes may impact biodiversity and ecosystem functions. Yet, there remains an important gap in meta-ecosystem models to predict multiple functions (e.g., carbon sequestration, elemental cycling, trophic efficiency) across ecosystem types (e.g., terrestrial-aquatic, benthic-pelagic). We derive a flexible meta-ecosystem model to predict ecosystem functions at landscape extents by integrating the spatial dimension of natural systems as spatial networks of different habitat types connected by cross-ecosystem flows of materials and organisms. We partition the physical connectedness of ecosystems from the spatial flow rates of materials and organisms, allowing the representation of all types of connectivity across ecosystem boundaries as well as the interaction(s) between them. Through simulating a forest-lake-stream meta-ecosystem, our model illustrated that even if spatial flows induced significant local losses of nutrients, differences in local ecosystem efficiencies could lead to increased secondary production at regional scale. This emergent result, which we dub the ‘cross-ecosystem efficiency hypothesis’, emphasizes the importance of integrating ecosystem diversity and complementarity in meta-ecosystem models to generate empirically testable hypotheses for ecosystem functions.