The advances in wearable/flexible electronics have triggered tremendous demands for flexible power sources, where flexible nanogenerators, capable of converting mechanical energy into electricity, demonstrate its great potential. Here, recent progress on flexible nanogenerators for mechanical energy harvesting toward self‐powered systems, including flexible piezoelectric and triboelectric nanogenerator, is reviewed. The emphasis is mainly on the basic working principle, the newly developed materials and structural design as well as associated typical applications for energy harvesting, sensing, and self‐powered systems. In addition, the progress of flexible hybrid nanogenerator in terms of its applications is also highlighted. Finally, the challenges and future perspectives toward flexible self‐powered systems are reviewed.