The complex tissue‐specific physiology that is orchestrated from the nano‐ to the macroscale, in conjugation with the dynamic biophysical/biochemical stimuli underlying biological processes, has inspired the design of sophisticated hydrogels and nanoparticle systems exhibiting stimuli‐responsive features. Recently, hydrogels and nanoparticles have been combined in advanced nanocomposite hybrid platforms expanding their range of biomedical applications. The ease and flexibility of attaining modular nanocomposite hydrogel constructs by selecting different classes of nanomaterials/hydrogels, or tuning nanoparticle‐hydrogel physicochemical interactions widely expands the range of attainable properties to levels beyond those of traditional platforms. This review showcases the intrinsic ability of hybrid constructs to react to external or internal/physiological stimuli in the scope of developing sophisticated and intelligent systems with application‐oriented features. Moreover, nanoparticle‐hydrogel platforms are overviewed in the context of encoding stimuli‐responsive cascades that recapitulate signaling interplays present in native biosystems. Collectively, recent breakthroughs in the design of stimuli‐responsive nanocomposite hydrogels improve their potential for operating as advanced systems in different biomedical applications that benefit from tailored single or multi‐responsiveness. Stimuli‐responsive nanocomposite hydrogels represent leading biofunctional platforms due to their design flexibility and ability to operate as intelligent devices that intrinsically recognize and react to physiological or external stimuli inputs. This review delineates recent trends in their design and assembly and critically overviews flagship hybrids on their path to attain sophisticated self‐regulating activities or serving as remote‐controlled long‐term therapeutic modalities.