Thiosemicarbazones are recognized for their flexibility in coordination and various applications in areas such as medicinal chemistry, catalysis, and material science. Thiosemicarbazone metal complexes are a significant area of study due to their intriguing properties and applications across multiple scientific fields. By using density functional theory (DFT) and molecular docking methods, researchers conduct computational studies to elucidate the structural, electronic, and reactivity characteristics of these complexes. These investigations not only aid in understanding experimental data but also guide synthetic strategies by offering predictive insights into the structural features of the complexes. Additionally, these computational approaches allow scientists to analyze electronic structures and spectroscopic properties, which is essential for elucidating reactivity patterns and establishing structure–activity relationships (SARs). In biological contexts, these studies provide insights into how these complexes interact with biological targets, enhancing our understanding of their mechanisms of action and informing the design of therapeutic agents that exhibit improved efficacy and decreased toxicity. Computational studies bridge the gap between experimental research and theoretical understanding, enabling scientists to predict and optimize the behavior of metal complexes in various chemical and biological systems. In this study, we discuss the computational insights of thiosemicarbazone metal complexes, exploring their structural properties, reactivity, and biomedical applications.