Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), not only affects the lungs but also damages various non-pulmonary organs, resulting in tissue injury and potential long-term sequelae in infected individuals. COVID-19 is likely to persist as a public health concern, given the frequent emergence of new mutations and viral strains. Multiple clinical lines of evidence indicate the efficacy of traditional Chinese medicine (TCM) in the prevention and treatment of COVID-19. However, the exact mechanism underlying these effects remains unclear. In this perspective review, we summarize the utility of in vitro three-dimensional (3D) cultured organoid models and organ-on-a-chip (OoC) technology for studying COVID-19 pathogenesis, viral tropism, and infectious mechanisms across different tissues. We highlight the successful application of these platforms in aiding drug development and discuss their advantages and limitations. We also review how such organotypic models can be employed to study TCMs. Finally, we discuss the opportunities for integrated microphysiological multi-tissue models to rapidly discover active components and potential targets in the context of COVID-19. The utilization of these emerging technologies could accelerate drug discovery and the modernization of TCM.