Inspired by the characteristics of cells in live organisms, new types of hybrids have been designed comprising live cells and abiotic materials having a variety of structures and functionalities. The major goal of these studies is to uncover hybridization approaches that promote cell stabilization and enable the introduction of new functions into living cells. Single-cells in nanoshells have great potential in a large number of applications including bioelectronics, cell protection, cell therapy, and biocatalysis. In this review, we discuss the results of investigations that have focused on the synthesis, structuration, functionalization, and applications of these single-cells in nanoshells. We describe synthesis methods to control the structural and functional features of single-cells in nanoshells, and further develop their applications in sustainable energy, environmental remediation, green biocatalysis, and smart cell therapy. Perceived limitations of single-cells in nanoshells have been also identified.