This article discusses the robust predefined output containment (RPOC) control problem for heterogeneous nonlinear multiagent systems having multiple uncertain nonidentical leaders. In order to solve this problem, a new kind of distributed observer-based RPOC control framework is presented. First, for obtaining the information of nonidentical leaders' dynamics, including uncertain parameters in leaders' system matrices, output matrices, states, and outputs, four kinds of adaptive observers are constructed in a fully distributed form without any knowledge of the dynamics of nonidentical leaders, exactly. Second, on the basis of adaptive learning technique, a new RPOC controller is then developed by using the presented observers, where the adaptive observers can make up for the uncertain parameter in followers' dynamics, and the solutions of output regulation equations can be obtained adaptively by the developed adaptive strategy. Furthermore, with the help of the output regulation method and Lyapunov stability theory, the RPOC criteria for the considered system under unknown nonidentical leaders' dynamics are derived from the constructed controller. Finally, a simulation example is provided to demonstrate the effectiveness of the proposed RPOC controller.