Intermolecular strain has long been used to steer and promote chemical reactions towards desired products in wet chemical synthesis. However, similar protocols have not been adopted for the on-surface synthesis on solid substrates due to the complexity of reaction processes. Recent advances in the sub-molecular resolution with scanning probe microscopy allow us to capture on-surface reaction pathways and to gain substantial insights into the role of strain in chemical reactions. The primary focus of this review is to highlight the recent findings on strain-induced on-surface reactions. Such substrate-induced processes can be applied to alter the chemical reactivity and to drive on-surface chemical reactions in different manners, which provides a promising alternative approach for on-surface synthesis. This review aims to shed light on the utilization of substrate-induced strain for on-surface transformation and synthesis of atomically-precise novel functional nanomaterials.