Laminar optical tomography (LOT) is a mesoscopic tomographic imaging technique ranging between confocal microscopy and diffuse optical tomography (DOT). Fluorescence LOT (FLOT) provides depth-resolved molecular information with 100-200μm resolution over 2-3mm depth. In this study, we use Monte Carlo simulation and singular-value analysis (SVA) to optimize the source-detector configurations for potential enhancement of FLOT imaging performance. The effects of different design parameters, including source incidence and detector collection angles, detector number, and sampling density, are presented. The results indicate that angled incidence/ detection configuration might improve the imaging resolution and depth sensitivity, especially for low-scattering medium. Increasing the number of detectors and the number of scanning steps will also result in enhanced imaging performance. We also demonstrate that the optimal imaging performance depends upon the background scattering coefficient. Our result might provide an optimization strategy for FLOT or LOT experimental setup.