As an emerging strategy for the synthesis of metal-organic frameworks (MOFs), a microdroplet-based spray method holds merits of improved heat and mass transfer rates, which allows the formation of MOF crystals in a much faster manner. To optimize the spray route for the MOF synthesis, further exploration is needed to understand the dominant variables controlling the quality of the products. With a series of experiments and advanced computational analysis, we present here general guidance for the synthesis of representative zeolitic imidazolate frameworks (i.e., ZIF-8 and ZIF-67) using the spray route. (c) 2021 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.