Abstract: This study provides a comprehensive review of Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) imaging, encompassing its fundamental principles, clinical applications, contemporary research, and future prospects for clinical translation. The section on foundational theory discusses the underlying physical mechanisms, the use of radiopharmaceuticals, and the technological evolution of imaging systems. Clinical applications are thoroughly examined across the three primary domains: cardiovascular, neurological, and oncological pathologies. Despite considerable advancements, persistent challenges remain in optimizing radiation doses, improving diagnostic accuracy, and achieving cost-effective implementation. Additionally, this review highlights the emerging potential of novel radiotracers for SPECT/CT imaging and explores its transformative role in radioligand-based theranostics and personalized medicine. By synthesizing current research, this review aims to serve as a comprehensive reference to guide future technological innovations and clinical applications of SPECT/CT imaging.