Heterogeneous catalysis is a surface phenomenon where the adsorption, desorption, and transfer of reactants and products are critical for catalytic performance. Recent results show that catalyst wettability is strongly related to the adsorption, desorption, and transfer of reactants and products. In this review, we briefly summarize strategies for regulating wettability to enrich reactants, accelerate the desorption of products, and promote mass transfer in heterogeneous catalysis. In addition, we explore insights into catalyst wettability for the enhancement of catalytic performance. Finally, the concerns and challenges in this subject are outlined, and practical strategies are proposed for the regulation of catalyst wettability. We hope that this review will be helpful for designing highly efficient heterogeneous catalysts in the future.