This study deals with the structural integrity of a co-axial octocopter cargo drone. Most unstable states in progress of various flight missions of the cargo drone are considered to be derived from take-off and landing operations. In order to evaluate the structural integrity of these states, three-dimensional FE (finite element) simulation using whole frame assembled with structural members and components is performed, and then the effective stress level and deflection degree are investigated. Also, topology optimization is adopted to improve the locally concentrated stress and large deflection around front and rear sections of the motor-support side member. From topology optimization, it is ensured that the shape and location of plate support have to be modified for improving the stress level and the deflection degree. Based on the optimized and modified feature, FE simulation is re-performed. Consequently, it is confirmed that the effective stress and the deflection are reduced to about 26.67% and 19.15% around the side member, respectively.