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The synthesis of drug substances (DS) requires the continuous effort of the pharma industry to ensure high sustainability standards. The Suzuki-Miyaura cross coupling is a fundamental C–C bond-forming reaction to produce complex DS intermediates. The present contribution points out the way in which the synthesis of DS intermediates by C–C cross coupling can be economically competitive, while minimizing waste by selecting the appropriate heterogeneous catalyst. By comparing homogeneous, immobilized heterogeneous catalysts on silica and metal–organic framework (MOF) catalysts, while considering the perspectives of academia and industry, the critical parameters for a successful industrial application of heterogeneous catalytic Suzuki-Miyaura cross coupling reactions were identified. Heterogeneous catalysts, such as MOFs, may provide a complementary platform for reducing waste and the costs of production related to such transformations.