The biological characteristics and microenvironmental changes at each stage of tissue repair are intricately linked, maintaining a dynamic spatiotemporal equilibrium. Monotherapies often fail to effectively address complex microenvironmental disturbances, but combining multiple factors (e.g., physical and chemical) represents a promising approach to enhance tissue regeneration and repair. However, there is a lack of comprehensive reviews that explore the efficacy and mechanisms of combining physical and chemical factors to promote repair. A multidimensional understanding of the spatiotemporal specificity in tissue repair, coupled with the integration of spatiotemporal regulation principles into the design of smart-responsive biomaterials, is essential for regulating the local microenvironment and maintaining dynamic equilibrium. Based on this, this review first discussed the pathophysiological characteristics of spatiotemporal changes in tissue repair associated with several diseases. Second, the advantages and disadvantages of the current means of spatiotemporal modulation of physical and chemical factors commonly used for tissue repair were summarized. Finally, therapeutic strategies that utilize smart response materials to modulate these changes through physical and chemical factors are outlined. In addition, current challenges and future prospects for the use of smart-responsive biomaterials in spatiotemporal regulation of tissue repair were discussed.