Rapid, on-the-spot diagnostic and monitoring systems are vital for the survival of patients with intracranial hematoma, as their conditions drastically deteriorate with time. To address the limited accessibility, high costs and static structure of currently used MRI and CT scanners, a portable non-invasive multi-slice microwave imaging system is presented for accurate 3D localization of hematoma inside human head. This diagnostic system provides fast data acquisition and imaging compared to the existing systems by means of a compact array of low-profile, unidirectional antennas with wideband operation. The 3D printed low-cost and portable system can be installed in an ambulance for rapid on-site diagnosis by paramedics. In this paper, the multi-slice head imaging system’s operating principle is numerically analysed and experimentally validated on realistic head phantoms. Quantitative analyses demonstrate that the multi-slice head imaging system is able to generate better quality reconstructed images providing 70% higher average signal to clutter ratio, 25% enhanced maximum signal to clutter ratio and with around 60% hematoma target localization compared to the previous head imaging systems. Nevertheless, numerical and experimental results demonstrate that previous reported 2D imaging systems are vulnerable to localization error, which is overcome in the presented multi-slice 3D imaging system. The non-ionizing system, which uses safe levels of very low microwave power, is also tested on human subjects. Results of realistic phantom and subjects demonstrate the feasibility of the system in future preclinical trials.