Anisotropic electronic and thermal transport properties can be harnessed to enhance the thermoelectric (TE) performance of materials. There is also a growing interest in exploring the functionality of single crystals, especially of materials with layered motifs, for thermoelectrics. Layered materials often exhibit anisotropic transport properties. Therefore, it is crucial to account for the anisotropy in transport properties in computational searches for TE materials. Traditional computational approaches are expensive and not amenable to high-throughput searches. In this work, we build upon our intutition from prior semi-empirical models to create a new anisotropic model of carrier mobility by utilizing the elastic stiffness and the conducitivity effective mass tensors. Similarly, we extend our prior semi-empirical lattice thermal conductivity model to account for anisotropy by calculating the speed of sound tensor. By combining the models for anisotropic mobility and lattice thermal conductivity, we predict the anisotropic TE performance quantified by the thermoelectric quality factor. We apply these models to predict the TE performance of a large number of layered materials (>2000) and identify candidates with predicted high performance.