The establishment of a comprehensive radiation oncology facility in India is a critical endeavor to address the rising cancer burden and improve patient outcomes. This paper provides a step-by-step guide for setting up a state-of-the-art radiation oncology department, emphasizing compliance with Atomic Energy Regulatory Board (AERB)1,4 regulations, optimal facility design, and seamless integration of advanced technologies. Key steps include site layout planning, AERB approvals, construction, equipment procurement, installation, commissioning, and operational licensing. The guide underscores the importance of early involvement of medical physicists and radiation safety officers to ensure regulatory adherence, safety, and efficiency. By incorporating best practices in radiation safety, quality assurance, and staff training, this paper aims to facilitate the creation of world-class radiation oncology centers that prioritize patient safety, operational excellence, and long-term sustainability.