Two-phase spray cooling has been an emerging thermal management technique offering high heat transfer coefficients and critical heat flux levels, near-uniform surface temperatures, and efficient coolant usage that enables to design of compact and lightweight systems. Due to these capabilities, spray cooling is a promising approach for high heat flux applications in computing, power electronics, and optics. Two-phase spray cooling inherently depends on saturation temperature-pressure relationships of the working fluid to take advantage of high heat transfer rates associated with liquid-vapor phase change. When a certain application requires strict temperature and/or pressure conditions, thermo-physical properties of the working fluid play a critical role in attaining proper efficiency, reliability, or packaging structure. However, some of the commonly used single-component working fluids have relatively poor properties and heat transfer performance. For example, water is the best coolant in terms of properties, yet in certain applications where the system operates at low temperature ambient, it cannot be implemented due to freezing risk. The common solution for this problem is to use the antifreeze mixtures (binary mixtures of water and alcohol) to reduce the freezing point. In such cases, utilizing binary mixtures to tune working fluid properties becomes an alternative approach. This study has two main objectives; (1) to experimentally investigate the two-phase spray cooling performance of water/2-propanol binary mixture, and (2) to numerically investigate the performance of an advanced heat spreader featuring high and directional thermal conductivity materials for high heat flux focal sources. The first part of the study involves experimental characterization of heat transfer performance. Tests are conducted on a small-scale, closed loop spray cooling system featuring a pressure atomized spray nozzle. The test section, made of copper, measures 10 mm x 10 mm x 2 mm with a plain, smooth surface. A cylindrical copper block, with a matching size square protrusion attached onto the back side of the test section, generates heat using cartridge heaters and simulates high heat flux source. Embedded thermocouples are used to determine the spray surface temperature. The working fluid, water/alcohol mixture, has various concentration levels of 2-propanol by mass fraction 0.0 (pure water), 0.25, 0.50, 0.879 (azeotrope) and 1.0 (pure alcohol)), representing both non-azeotropic and azeotropic cases. Spray cooling tests are performed with a constant flow rate of 5.6 ml/cm2.s at subcooled temperatures (̃20oC) and atmospheric pressure. Experimental procedure involves controlling the heat flux in increasing steps, and recording the corresponding steady-state temperatures to obtain cooling curves in the form of surface superheat vs. heat flux. The second part of the study investigates an advanced heat spreader design for thermal management of a high heat flux focal source. The heat spreader comprises of three layers: a copper layer that interfaces with the heat source, a high and directional thermal conductivity material (such as CVD diamond and Pyrolytic graphite) layer, and another copper layer that is exposed to two-phase spray cooling. The analysis applies various heat fluxes on the heat source side and the experimentally obtained heat transfer coefficients on the spray side of the spreader design to determine the temperature and heat flux distributions, and examine the potential capabilities of this configuration.