One measurement-based dynamic optimization scheme can achieve optimality under uncertainties by tracking the necessary condition of optimality (NCO-tracking), with a basic assumption that the solution model remains invariant in the presence of all kinds of uncertainties. This assumption is not satisfied in some cases and the standard NCO-tracking scheme is infeasible. In this paper, a novel two-level NCO-tracking scheme is proposed to deal with this problem. A heuristic criterion is given for triggering outer level compensation procedure to update the solution model once any change is detected via online measurement and estimation. The standard NCO-tracking process is carried out at the inner level based on the updated solutionmodel. The proposed approach is illustrated via a bioreactor in penicillin fermentation process. (C) 2014 The Chemical Industry and Engineering Society of China, and Chemical Industry Press. All rights reserved.