A luminescent solar concentrator (LSC) offers a viable solution to spectrally convert and concentrate both direct and diffuse sunlight without the need for tracking. Its potential for commercialization is currently limited by the optical performance. A detailed understanding of the effects of both waveguide and luminophore properties is crucial for designing efficient LSCs. Herein, a self-consistent modelling framework of radiative transfer in LSCs is presented to analyze these effects by incorporating all properties at multiple length scales. A modified radiative transfer equation (RTE) is derived capturing the requirement that both photon absorption and photoluminescence quantum yield (PLQY) should occur simultaneously to trigger the PL emission. The Monte Carlo method is used to solve this modified RTE along with its boundary conditions. This framework is further employed to investigate the performance of LSCs doped with Lumogen F Red 305 (LFR305) dye. For the realistic scenarios, the transmission loss forms the main loss mechanism and accounts for 72.6–92.1% depending on the specific dimensions and LFR305 doping. An external photon efficiency of 13.0% is predicted for an LSC of 20 × 20 × 0.5 cm3 with a dye concentration of 5 × 10−4 mol/L. As to the hypothetical scenarios, the waveguide refractive index affects both the top reflection and the escape cone losses, while in contrast, the PLQY and the Stokes shift mainly affect the QY loss. Future efforts on LSC optimization should be directed towards reducing the transmission loss.