<p>Autophagy is one of the best-characterized “pro-survival” pathways, which, paradoxically, in its extreme activation, can lead to cell death. Under conditions of moderate physiological disturbances, autophagy plays a crucial role in maintaining homeostasis within the human organism. Currently, in the context of treating cancer, researchers are exploring novel methods to modulate autophagic processes. Nanomedicine, which leverages nanoparticles (NPs) for targeted therapies, has become a prominent focus in numerous scientific studies. It has been observed that NPs can be employed to either stimulate or inhibit autophagic processes. Due to their diverse physicochemical properties, nanomaterials can influence cellular compartments directly involved in autophagy. This review examines the multifaceted effects of nanoparticle exposure on autophagy, with a focus on mechanisms that deviate from the classical autophagic flux. By dissecting the molecular crosstalk between nanomaterials and autophagy-related signaling networks, we aim to elucidate how NPs reshape cellular behavior and contribute to therapeutic outcomes in malignancy. Particular attention has been directed toward significant challenges in determining whether autophagy activation exerts protective or deleterious effects on cancer cells. A comprehensive understanding of the effects of nanotechnology-driven autophagy on biological systems could yield groundbreaking discoveries for advanced strategies in combating cancer and other proliferative diseases.</p>