In this work, intermittent spray cooling is proposed as a new technological concept to remove heat fluxes with good performance and introduce the potential use of advanced control techniques in the development of thermal management systems. The objective of this research work is to provide further insight into the physics involved in the heat transfer process triggered by the impact of an intermittent spray, and further investigate the effects of injection system parameters, such as the frequency of injection, pulse duration, initial wall temperature, pressure of injection and impingement distance, on the intermittent cooling system’s performance. The results include a brief description of the spray intermittent behavior, an analysis on its thermal response and an evaluation of its performance. The “duty cycle”, defined as the percentage of the cyclic time during which the cooling liquid is injected, is found to be the main parameter enabling a more accurate control of the cooling process. The experiments reported evidence that small duty cycles promote heat removal by phase-change. With larger duty cycles, the effect of reducing the time lag between consecutive injections is a greater interaction between cycles, eventually leading to the formation of a thin liquid film. As the duty cycle evolves toward the continuous spray condition, the cooling system’s thermal response improves, but phase-change is mitigated, affecting the system’s performance. Intermittent spray cooling is also compared with continuous spray cooling experiments and liquid savings has been estimated by 10–90% for the same energetic efficiencies reported in the literature. Finally, general guidelines are outlined for the design of thermal management systems based on intermittent spray cooling.