<p>Conventional food packaging research primarily treats degradation products as undesirable outcomes that must be blocked, absorbed, or neutralized. As a result, packaging materials are commonly designed to resist spoilage processes rather than to engage with them. This review introduces a novel conceptual framework that positions food-derived degradation products as fundamental design inputs for next-generation packaging materials. Instead of relying on external additives, indicators, or electronic sensors, the proposed approach integrates degradation chemistry directly into material selection, structure, and functional behaviour. Spoilage metabolites are examined as predictable and system-specific signals capable of inducing targeted material responses, including selective permeability modulation, interfacial transformations, controlled sorption, and mechanical adjustments such as softening or stiffening. By aligning packaging behaviour with the inherent degradation pathways of different food matrices, materials can be engineered to respond proportionally and often irreversibly to actual quality deterioration rather than generalized storage conditions such as time–temperature histories. The review consolidates dispersed insights from food chemistry, polymer science, biopolymer engineering, and surface/interface science to establish degradation-informed design principles for packaging systems. By reframing spoilage by-products as functional constraints and opportunities, this perspective advances a co-evolutionary model of food–material interactions. Such an approach has significant implications for shelf-life communication, waste reduction, and the development of sustainable, intrinsically food-responsive packaging materials that operate without additional chemicals, electronics, or labelling technologies.</p>