Government and societal interests in additive manufacturing have increased scrutiny on process analysis, cross-cutting sustainability, and integrated decision-making methods to address commercialization and sustainability challenges. One of the key challenges is the absence of standardized metrics to assess design parameters and manufacturing practices. The primary objective of this research is to create a knowledge-based multi-criteria decision-making framework for enhancing sustainability across the design and fabrication of medical devices. The motivation behind this study lies in the inherent limitations of the existing methods. The proposed framework herein improves the traditional approaches by integrating extensive sharing of information and feedback among all design and manufacturing steps, and consequently coupling the economic and environmental sustainability dimensions. The framework includes sets of qualitative (e.g., data processing and design analysis) and quantitative (e.g., build time and energy use analyses) methods to assess transforming the raw material into optimal and sustainable final products. As an application of this study, optimal and sustainable approaches for the developing and competitive market of Orthotic and Prosthetic, particularly Ankle Foot Orthosis (AFO), is examined. Decision makers, such as managers and manufacturers, will benefit from the integrated methods in the proposed framework. The results indicate the framework offers a promising approach to address existing sustainability challenges in the AFO industry.