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Configuration similarity is a special form of content-based image retrieval that considers relative object locations. It can be used as a standalone method, or to complement retrieval based on visual or semantic features. The corresponding queries ask for sets of objects that satisfy some spatio-temporal constraints, e.g., "find all triplets of objects (v1, v2, v3), such that v1 is northeast of v2, which is inside v3." Exhaustive processing (i.e., retrieval of the best solutions) of configuration similarity queries, in general, has exponential complexity and fast search for sub-optimal solutions is the only way to deal with the vast amounts of multimedia information in several real-time applications. In this paper we first discuss the utilization of nonsystematic search heuristics, based on genetic algorithms, simulated annealing and hill climbing approaches. An extensive experimentation with real and synthetic datasets reveals that hill climbing techniques are the best for the current problem; therefore, as a subsequent step we study the search space, and develop improved variations of hill climbing that take advantage of the special structure of the problem to enhance speed. The proposed heuristic methods significantly outperform systematic search when there is only limited time for query processing.