Cerenkov luminescence tomography (CLT) is a promising tool that enables three-dimensional noninvasive in vivo detection of radiopharmaceuticals. Conventionally, multispectral information and diffusion theory were introduced to achieve whole-body tomographic reconstruction. However, the diffusion theory inevitably causes systematic error in blue bands of the electromagnetic spectrum due to high-tissue absorption, and CL has a blue-weighted broad spectrum. Therefore, it is challenging to improve the accuracy of CLT. The performance of the -order simplified spherical harmonics approximation (SPn) in different spectra is evaluated, and a multispectral hybrid CLT based on the combination of different SPn models is proposed to handle the Cerenkov photon transport problem in complex media. The in vivo xenograft experiment shows that this approach can effectively improve the quality and accuracy of the reconstructed light source. We believe that the new reconstruction method will advance the development of CLT for more in vivo imaging applications.