In this review, we outline examples that illustrate the design criteria for achieving macromolecular assemblies that incorporate a combination of two or more chemical, physical or biological stimuli-responsive components. Progress in both fundamental investigation into the phase transformations of these polymers in response to multiple stimuli and their utilization in a variety of practical applications are highlighted. Using these examples, we aim to explain the origin of employed mechanisms of stimuli responsiveness which may serve as a guideline to inspire future design of multi-stimuli responsive materials.