One of the major issues in tissue engineering is regulation of stem cell differentiation toward specific lineages. Unlike biological and chemical signals, physical signals with adjustable properties can be applied to stem cells in a timely and localized manner, thus making them a hot topic for research in the fields of biomaterials, tissue engineering, and cell biology. According to the signals sensed by cells, physical signals used for regulating stem cell fate can be classified into six categories: mechanical, light, thermal, electrical, acoustic, and magnetic. In most cases, external macroscopic physical fields cannot be used to modulate stem cell fate, as only the localized physical signals accepted by the surface receptors can regulate stem cell differentiation via nanoscale fibrin polysaccharide fibers. However, surface receptors related to certain kinds of physical signals are still unknown. Recently, significant progress has been made in the development of functional materials for energy conversion. Consequently, localized physical fields can be produced by absorbing energy from an external physical field and subsequently releasing another type of localized energy through functional nanostructures. Based on the above concepts, we propose a methodology that can be utilized for stem cell engineering and for the regulation of stem cell fate via nanostructure-mediated physical signals. In this review, the combined effect of various approaches and mechanisms of physical signals provides a perspective on stem cell fate promotion by nanostructure-mediated physical signals. We expect that this review will aid the development of remote-controlled and wireless platforms to physically guide stem cell differentiation both in vitro and in vivo, using optimized stimulation parameters and mechanistic investigations while driving the progress of research in the fields of materials science, cell biology, and clinical research.