Herein, a series of thermoplastic polyurethane (TPU)/carbomer (CB)/nano-celluloses (CNCs) multi-responsive shape-memory nanocomposite films were tailored using CNCs as a crosslinker. The impact of CNCs content on the mechanical properties of the TPU/CB/CNC nanocomposite films has been comprehensively studied by which the best CNCs loading was reported at 5 wt%. The chemistry and microstructure of the nanocomposite film have been precisely elucidated by FT-IR spectroscopy, 1H NMR spectrum, XRD, and DSC to verify the reaction of –CO-NH– in TPU with –COOH in CB—forming quaternary ammonium ionic and hydrogen bonds. The shape-memory properties of the TPU/CB/CNC nanocomposite film were also investigated in different conditions such as water, ethanol, acid, alkali, and heat. Moreover, the shape recovery behavior of the nanocomposite film was examined by changing pH, which affects the quaternary ammonium ionic and hydrogen bonds as switch units. Although the shape of the thin nanocomposite film has successfully recovered in the alkaline environment, the internal structure was damaged. After transfer to the acidic environment, the destroyed internal structure of the strip was revived, and its strength improved to carry a foolproof load. Eventually, the as-made nanocomposite film has a multi-responsive capability against water, ethanol, pH, and heat, representing its potential in slow-release drug and flexible robotic as well as electronic applications.