Natural barriers, encompassing stable geological formations that serve as the final bastion against radionuclide transport, are paramount in mitigating the long-term contamination risks associated with the nuclear waste disposal. Therefore, it is important to simulate and predict the processes and spatial-temporal distributions of radionuclide transport within these barriers. However, accurately predicting radionuclide transport on the field scale is challenging due to uncertainties associated with parameter scaling. This study develops an integrated evaluation framework that combines upscaled parameters, streamline transport models, and response surface techniques to systematically assess environmental risk metrics and parameter uncertainties across different scales. Initially, upscaling methods are established to estimate the prior interval of critical transport parameters at the field scale, and streamline models are derived by considering the radionuclides transport with a variety of physicochemical mechanisms and geological characterizations in natural barriers. To assess uncertainty ranges of the risk metrics related to upscaled parameters, uncertainty quantification is performed on the ground of 5000 Monte Carlo simulations. The results indicate that the upscaled dispersivity of fractured media (αLf) has a relatively high sensitivity ranking on release dose for all nuclides, and upscaled matrix sorption coefficient (Kd) of Pu-242 strongly affects breakthrough time and release dose of Pu-242. Facilitated by robust response surface with the lowest R2 of 0.89, it is shown that the release doses of Pu-242 and Pb-210 increase under conditions of low Kd and αLf, respectively. Furthermore, statistical analysis reveals that employing limited laboratory-scale parameters results in narrower confidence intervals for risk metrics, while upscaling methods better account for the highly heterogeneous properties of large-scale field conditions. The developed risk evaluation framework provides valuable insights for utilizing upscaled parameters and modeling radionuclide transport within natural barriers under various scenarios.