Advancements in material science, manufacturing and sensor technologies, Artificial Intelligence, and the Internet of Things have paved the way for fabricating new parts using additive manufacturing in microgravity conditions. NASA has successfully demonstrated 3D printing onboard the International Space Station (ISS), though at a minor scale. Nevertheless, the parts built onboard the ISS were returned to Earth for further testing and verification. The logistics of bi-directional transportation of raw materials from Earth to ISS and 3D-printed parts from ISS back to Earth is complex, expensive, and slow. Harnessing materials from space to establish in-orbit manufacturing as a sustainable process is both technically and economically challenging. The potential to reuse, repurpose or recycle space debris is not well studied, though there is an increasing momentum in Active Debris Removal (ADR) missions. Unlike the standard research or review paper, this is a visionary paper in which the authors explicitly address the intersection between space debris removal and in-space manufacturing. This paper defines a pathway towards implementing an operational in-orbit manufacturing and debris removal model. For the first time, the authors introduce the application of Cloud-Based Design and Manufacturing (CBDM) for in-space manufacturing in this paper. The paper aims to define a roadmap towards implementing a space operational model for in-orbit manufacturing and debris removal. Future enabling technologies that will leverage the advances in robotics, automation, and Space 5.0-based solutions to create a new environmentally friendly and economically profitable orbital ecosystem are presented. The authors analyze the pros and cons of robotic ADR, upcycling and recycling space debris for on-demand manufacturing in orbit and present a systematic approach to implementing in-orbit manufacturing as a new frontier. Recommendations are made to establish an imminent Earth-independent space logistics and supply chain system for operating an orbital factory or warehouse that will help realize a suite of in-orbit manufacturing, maintenance, and assembly missions.