A true challenge in designing multiresponsive complex macro-molecular architectures is to tune their conformation at will by changing the gradients of external stimuli. However, the lack of a clear molecular-level understanding, establishing a delicate interplay between segment-based interaction details and large-scale macromolecular properties, has hindered the implementation of design principles for a long time. Combining molecular simulations, together with complementary polymer synthesis and characterization, we propose a molecular-level design principle of multiresponsive copolymer architectures. For this purpose, we use the co-nonsolvency concept that is associated with polymer collapse in miscible good solvents. We show how the responsiveness of different polymer blocks can provide fully flexible conformational tuning and, therefore, may serve as a guiding principle for smart material design.