Extensive efforts have been made to integrate diffuse optical tomography (DOT) with other imaging modalities, such as magnetic-resonance imaging and x-ray computerized tomography, for its performance improvement. However, the experimental apparatus is in general intricate and costly due to adoption of the physically distinct radiation regimes. In this study, a time-domain fluorescence-guided DOT methodology that incorporates a priori localization information provided by diffuse fluorescence tomography (DFT) is investigated in an attempt to optimize recovery of the optical property distributions. The methodology is based on a specifically designed multichannel time-correlated single-photon-counting DOT/DFT system as well as a featured-data image reconstruction scheme that is developed within the framework of the generalized pulse spectrum technique and employs the third-order simplified harmonics approximation to the radiative transfer equation as the forward model. We have validated the methodology using phantom experiments and demonstrated that, with the guidance of fluorescence a priori, the quantitativeness and spatial resolution of the recovered optical target can be considerably improved in terms of the absorption and scattering images.