Abstract: The application of concrete-filled steel tubular (CFST) mega-columns in supertall structures has become increasingly widespread. However, the enlargement of steel tube cross-sections significantly increases the difficulty of construction quality control. This study focuses on a CFST mega-column with severe misalignment defects in a super high-rise project. The column with the most critical misalignment was selected as the research object. Using ABAQUS finite element software, the mechanical performance of the column under eccentric compression and horizontal unidirectional loading was simulated under varying misalignment magnitudes and eccentricities. Results indicate that the influence of existing misalignment defects on the column's mechanical behavior remains within an acceptable range. Subsequently, general reinforcement solutions were proposed for two scenarios: misalignment exceeding 8 mm and misalignment ranging from 3 mm–8 mm. Local computational models were established to compare three working conditions: no misalignment, misalignment without reinforcement, and misalignment with reinforcement. By analyzing stress nephograms and load-displacement curves, the effectiveness of the proposed reinforcement measures were validated, and the optimal reinforcement method for the most severe misalignment scenario was identified. Subsequent construction should ensure that the construction quality of CFST columns meets regulatory requirements through strict control of processing quality, on-site acceptance, and on-site assembly processes.