Biological systems operate through a tightly regulated network of electrical, chemical, and mechanical signals; consequently, dysregulated signaling cascades underlie pathologies across nervous, immune, and oncological systems. While traditional therapeutic approaches have relied on the passive transport of active agents or invasive monitoring tools, the ability to perturb these systems with spatiotemporal precision remains a critical challenge. This review examines remotely responsive nanoplatforms that harness external energy, such as ultrasound, magnetic fields, and light, to drive localized physical stimulation and in situ chemical synthesis, thereby establishing both as promising avenues for targeted therapy.