The present work is concerned with the numerical investigation of thermal response of biological tissue phantoms during laser-based photo-thermal therapy for destroying cancerous/abnormal cells with minimal damage to the surrounding normal cells. The synthetically generated two-dimensional tissue phantoms have been irradiated with a short pulse laser and light-tissue interaction has been modeled using transient radiative transport equation (RTE). Discrete ordinate method (DOM) has been employed to solve the complete transient radiative transport equation. Biological tissue phantoms with and without the presence of single and/or multiple inhomogeneities have been considered. Optical inhomogeneities of different nature and varying contrast levels (ratio of optical properties of the inhomogeneity and that of the background medium) have been considered to numerically simulate the abnormal cells embedded in an otherwise homogenous medium. In order to determine the two-dimensional temperature distribution inside the tissue medium, the RTE has been coupled with Penne's bio-heat transfer equation which has been solved using finite volume method. The RTE-based numerical code developed in the present work has been benchmarked against the results published in the literature for the same operating parameters. Thereafter, the effects of varying contrast levels of the embedded inhomogeneity, nature of the inhomogeneity (absorbing/scattering), laser pulse amplitude, etc. on the resultant temperature distribution inside the tissue phantoms have been reported. Based on the primary findings of the study, safe laser parameters (e.g. amplitude of laser pulse) for a given set of absorption and scattering coefficients have been reported. (C) 2014 Elsevier Ltd. All rights reserved,