Fluorescence lifetime imaging offers the unique ability to monitor the molecular status of the tissue microenvironment. However, the scattering nature of tissues remains a challenge for mesoscopic 3D high resolution imaging. We introduce the design of a mesoscopic light-sheet system with short-wave infrared (SWIR) intensity and near infrared (NIR) fluorescent lifetime imaging capabilities. This system enables 3D mesoscopic imaging of high-resolution probe biodistribution and fluorescent lifetime. The system was characterized and validated through phantom experiments, and further tested on tumor spheroids and ex vivo organ samples.