Calcium sulfide (CaS) is a widely investigated alkaline earth sulfide nanophosphor with promising applications in optoelectronics and biomedical fields due to its excellent photoluminescence properties. The selection of the synthesis method is a crucial factor in determining the efficacy of nanophosphors for various applications. This review provides a comprehensive overview of the various synthesis techniques employed to develop CaS nanophosphors, including solvothermal, alkoxide, sol-gel, microwave, wet chemical co-precipitation, solid-state diffusion, and single-source precursor methods. The structural and optical properties of CaS nanophosphors are discussed in detail, highlighting the influence of different dopants on the emission color, which can be tuned from blue to red. The review also explores the potential applications of CaS nanophosphors in optoelectronics and biomedicine. This review serves as a valuable resource for researchers interested in developing CaS nanophosphors for various optoelectronic and biomedical applications, providing insights into the latest advancements and future prospects in this field.