There has been an increasing interest in uncovering smuggled nuclear materials associated with the War on Terror. Detection of special nuclear materials hidden in cargo containers is a major challenge in national and international security. We propose a new physics-based method to determine the presence of the spectral signature of one or more nuclides from a poorly resolved spectra with weak signatures. The method is different from traditional methods that rely primarily on peak finding algorithms. The new approach considers each of the signatures in the library to be a linear combination of subspectra. These subspectra are obtained by assuming a signature consisting of just one of the unique gamma rays emitted by the nuclei. We propose a Poisson regression model for deducing which nuclei are present in the observed spectrum. In recognition that a radiation source generally comprises few nuclear materials, the underlying Poisson model is sparse, i.e. most of the regression coefficients are zero (positive coefficients correspond to the presence of nuclear materials). We develop an iterative algorithm for a penalized likelihood estimation that prompts sparsity. We illustrate the efficacy of the proposed method by simulations using a variety of poorly resolved, low signal-to-noise ratio (SNR) situations, which show that the proposed approach enjoys excellent empirical performance even with SNR as low as to -15db. The proposed method is shown to be variable-selection consistent, in the framework of increasing detection time and under mild regularity conditions. We study the problem of testing for shielding, i.e. the presence of intervening materials that attenuate the gamma ray signal. We show that, as detection time increases to infinity, the Lagrange multiplier test, the likelihood ratio test and Wald test are asymptotically equivalent, under the null hypothesis, and their asymptotic null distribution is Chi-square. We also derived the local power of these tests. We also develop a nonparametric approach for detecting spectra indicative of the presence of SNM. This approach characterizes the shape change in a spectrum from background radiation. We do this by proposing a dissimilarity function that characterizes the complete shape change of a spectrum from the background, over all energy channels. We derive the null asymptotic test distributions in terms of functionals of the Brownian bridge. Simulation results show that the proposed approach is very powerful and promising for detecting weak signals. It is able to accurately detect weak signals with SNR as low as -37db.