A laser-driven flyer impact system was constructed, characterized, and validated for performing uniaxial-strain experiments to investigate the shock equation-of-state (EOS) and processes leading to reaction initiation in thin, fully-dense Ni-Al nanolayered foils. Additionally, various fully-dense Ni-Al mixtures with highly heterogeneous microstructures and widely varying length scales were investigated to understand influence of meso-scale features on the shock compression and reaction response. Ni-Al composites are a class of reactive materials also called Structural Energetic Materials (SEMs), which aim to combine stiffness and strength with the ability to release large amounts of energy through highly exothermic reactions when the constituents are intimately mixed during shock loading. While porous reactive materials have been studied extensively, the processes leading to reaction initiation in fully-dense mixtures consisting of phases with disparate mechanical properties is more ambiguous. A table-top, small-scale laser system was developed for studying shock-induced effects in extremely thin reactive materials. Laser accelerated thin foil impact experiments utilizing time-resolved interferometry allowed for measuring the Hugoniot of the nanolayered Ni-Al foil over a range of particle velocities/pressures. Separate recovery experiments were performed by shock-loading Ni-Al foils slightly below the reaction initiation threshold and performing post-mortem TEM/STEM analysis to identify the constituent mixing processes leading to reaction. Direct-shock experiments were performed on the different fully-dense Ni-Al mixtures and hydrodynamic simulations using real microstructures allowed direct correlations with the experiment results, which yielded an improved understanding of the effect of phase arrangement on the shock propagation and reaction initiation response. The EOS experiments performed at particle velocities > 200 m/s showed a deviation from the predicted inert trend and recovered targets showed complete reaction to the B2-NiAl intermetallic phase. The measured deviation from inert behavior and state of recovered material suggests the occurrence of a shock-induced chemical reaction. The shocked (but unreacted) Ni-Al materials contained distinct constituent mixing features (layer jets and intermixed zones), where significant elemental penetration occurred and are likely sources of reaction initiation. The observed results provide the first clear evidence of shock-induced reactions in fully-dense nanolayered Ni-Al foils.