Spatial management has been adopted worldwide to mitigate habitat impacts while achieving fisheries management objectives. However, there is little theory or practice for predicting the impact of spatial regulations on future fishery production; this would provide scientific basis for greater flexibility in fisheries management when balancing fishery and conservation goals. We propose that predicting changes in fishery production resulting from human activities within specific habitats is a Grand Challenge for habitat science in the coming decade(s). We then outline three difficulties in resolving this Grand Habitat Challenge, including: (i) stage-structured responses to habitat impacts, (ii) nonlocal responses, and (iii) mechanistic associations among habitat variables. We next discuss analytical approaches to address each difficulty, respectively: (i) ongoing developments for spatial demographic models; (ii) individual movement models and rank-reduction approaches to identify regional variability; (iii) causal analysis involving structural equation models. We demonstrate nonlocal effects in detail using a diffusion-taxis movement model applied to sablefish (Anoplopoma fimbria) in the Gulf of Alaska and discuss all three approaches for deep-sea corals. Despite isolated progress to resolve individual difficulties, we argue that resolving this Grand Habitat Challenge will require a coordinated commitment from science agencies worldwide.