Due to its complexity, sterilization has been perceived by some professionals who lack sterility assurance expertise as a “black box” process. Historically, medical device manufacturers have selected one of the available industrial sterilization options: dry heat, moist heat, gamma, or ethylene oxide (EO). The preselection of a sterilization modality (method) typically is made without understanding its impact based on qualified sterilization processes for existing products, capability, or resources required for the specific processes. Early engagement with sterilization subject matter experts (SMEs) can redirect the decision to preselect a legacy modality and help foster innovation and operational agility. Recent focus on supply chain flexibility and sustainability by the medical device industry has been affected by concerns surrounding cobalt-60 shortages and EO emissions. These factors drive the need for early involvement with sterility assurance SMEs in the product development process and the exploration of multiple sterilization modalities. This article highlights the importance of exploring multiple sterilization modalities during the product development stage to support sustainable business continuity plans.