Nanoparticle drug-delivery systems are commonly designed through controllable material attributes, yet the identity governing their biological performance is altered as soon as they encounter complex physiological environments. This mismatch between engineered specification and acquired biological behavior complicates computational design, formulation optimization, safety assessment, and manufacturing translation. This article develops an original nanomedicine design-space theory for reasoning at that unstable boundary. The proposed Unstable Nano-Design Boundary treats a nanoparticle not as a fixed object but as a context-dependent sequence of states produced by interactions among engineered identity, biological context, acquired interfacial identity, immune and transport selection, and the manufacturability envelope. The approach integrates evidence on protein-corona formation, colloidal transformation, targeting disruption, process-dependent critical quality attributes, scale-up constraints, and multivariate formulation design. Its central contribution is a bounded design-space construct in which delivery, safety, manufacturability, and uncertainty must be evaluated jointly rather than collapsed into a single performance measure. The theory also distinguishes nominal formulation control from biological state control and separates computational prioritization from experimental confirmation and product reproducibility. The construct is not presented as an empirically validated model, universal taxonomy, regulatory criterion, or deployment-ready decision system. Its applicability remains conditional on material class, payload, route, disease state, host variability, exposure history, analytical method, and manufacturing platform. By making these dependencies explicit, the proposed framework may support more defensible model development, evidence mapping, experimental design, and translation planning for nanoparticle medicines.