Recently, metal-clad leaky waveguides (MCLW) have been proposed as highly sensitive single point sensor devices for small-volume refractive index (RI) and fluorescence detection. In this paper, we present a theoretical study of the efficiency of MCLW-based sensors on glass substrate, for fluorescence detection. It is shown that MCLWs can be designed in order to obtain an efficient coupling of fluorescence emission with their leaky modes. This leads to a higher directionality of the fluorescence emission into the glass substrate, when compared to the emission near a pure glass/water interface and surface-plasmon coupled emission (SPCE). Numerical analyses also indicate that collecting the fluorescence emission through a water-immersed microscope objective, may result in a 70-fold enhancement of the detectable signal when compared to conventional fluorescence detection carried out on a glass slide.