This study presents a simulation-driven methodology for the design and optimization of a lightweight drone frame. Starting with a CAD model developed in SolidWorks, finite element analysis (FEA) and computational fluid dynamics (CFD) which are used to evaluate stress, deformation, fatigue behavior, and aerodynamic performance. Topology optimization is then applied to reduce non-critical material and enhance the stiffness-to-weight ratio. CFD-informed refinements further help to minimize drag and improve airflow uniformity. The final design is fabricated using fused deposition modeling (FDM) with PLA, enabling rapid prototyping and experimental validation. Future work will explore advanced materials to improve fatigue resistance and structural durability.