Nanostructured heterogeneous energetic materials are a class of high-energy materials that utilize intimately mixed fuel and oxidizer particles to rapidly release a large amount of stored chemical energy in the form of heat, light, and intense pressures. Developing robust and scalable strategies to modify the structural features of these materials to tailor their energy release behavior is paramount to their success in large-scale propellant applications, which demand a consistent and predictable delivery of the stored material energy. This dissertation explores a multi-scale structure modification (nano-micro-macro) approach to achieve tunability in the functional energetic properties of reactive metal-based nanoscale fuels. Specifically, I have developed scalable aerosol- and laser-assisted techniques for the synthesis and assembly of nanostructured reactive metals, alloys, and their composites. This dissertation also identifies key fabrication, design, and assembly parameters that enable the tuning of material structural features such as particle size, composition, aggregate morphology, microstructure, and porosity. Additionally, the role of these structural modifications on their functional properties such as energy density, oxidation behavior, reaction pathways, ignition, and energy release characteristics has been extensively studied. Therefore, through these investigations, the dissertation establishes the critical process design-structure-property-function relationships in metal-based fuel systems. To achieve structural and reaction control on the nanoparticle scale, three strategies are explored. First, a vapor-phase route to surface-pure, core−shell nanoscale magnesium particles (Mg NPs) is employed, whereby controlled evaporation and growth are used to tune nanoparticle sizes and their size-dependent oxidation and energy release behavior are evaluated. Through direct observations from extensive in situ characterizations, I demonstrate that the remarkably high reactivity of Mg NPs (up to 10-fold higher than Al NPs) is a direct consequence of enhanced vaporization and Mg release from their high-energy surfaces that result in the accelerated energy release kinetics from their composites. Secondly, the synergistic role of Mg NP additives in inducing heterogeneous etching reactions on the surface of boron nanoparticles is studied. Specifically, I show that Mg NPs rapidly release vapor-phase Mg (~100 µs), which reacts exothermically (∆H_r= -420 kJ mol-1) with the molten B2O3 layer and assists in its removal during the reaction, causing ~6-fold reactivity enhancement and ~60% reduction in the burn times of boron. A third approach utilizes an in-flight surface modification of Mg NPs with a reactive element (Si) to form core-shell Mg-Si nanoparticles. Through mechanistic investigations of these systems, I find that the Si-coated Mg NPs themselves undergo an intraparticle condensed-phase alloying reaction between the Mg core and Si shell at relatively low-temperatures (400-500°C), resulting in highly accelerated reaction rates (~3-9-fold shorter reaction timescales) and lower ignition temperatures (~210°C lowering) than unfunctionalized Mg particles. Next, two aerosol-phase assembly techniques are explored to control the micron-scale structural and aggregation features of metal nanoparticle assemblies. First, an electrospray approach is used to incorporate plasma-synthesized ultrasmall Si particles to fill in the void structure of Al-based microparticles to augment their volumetric energy density and reactivity. This approach results in ~21% enhancement in energy density due to partial filling of structural voids and ~2-3-fold enhancement of reaction rates due to enhanced transport in ultrafine silicon particles. Another vapor-phase assembly approach employing external magnetic fields during synthesis is explored in directing the in-flight assembly of ferromagnetic metal nanoparticles into distinct aggregate morphologies with altered fractal dimensions. For control over the macroscale features of nanostructured composites, three robust and scalable techniques are employed. The first method utilizes spray drying as a highly scalable approach (production rates up to ~275 g h-1) to assemble metal and oxidizer nanoparticles into microparticle composites with ~2-7-fold higher reactivities than their physically mixed counterparts as a result of rapid gas generation and reduced nanoparticle sintering. I further demonstrate that these nanostructured microparticles can be further processed and additively manufactured into macroscale, hierarchical films (macro-micro-nano) without compromising their structural integrity. The third technique I have developed for macroscale structure modulation is by employing spatially and temporally resolved CO2 laser pulses to fabricate and write a high concentration of unaggregated, sub-10 nm metal nanoparticles directly in polymer films. Using this approach, I demonstrate that laser parameters – pulse duration, laser energy flux, and pulsed thermal loads – can be used for direct, in-situ modulation of particle size distributions of metal nanoclusters in polymer matrices. Rapid heating timescales employed in this approach allow for the scalable manufacturing and structural control of metal nanoclusters with production rates up to 1 g min-1. In conjunction with each other, all three techniques enable high-yield manufacturing of metal-based composites with a broad, nano- to macro-scale structural control. Finally, the structure and reaction modulation strategies are suggested for other fuel systems such as nanoscale reactive alloys (Al-Mg) to achieve controllable energy release behavior through further modifications of fuel composition and morphological features. The techniques developed in this dissertation will allow the strategic design of metal-based nanostructured energetic composites with tailored energy release rates and controllable structural features over a wide range of length scales.