Most feedback perimeter control approaches that are based on the Macroscopic Fundamental Diagram (MFD) and are tested in detailed network structures restrict inflow from the external boundary of the network. Although such a measure is beneficial for the network performance, it creates virtual queues that do not interact with the rest of the traffic and assumes small unrestricted flow (i.e. almost zero disturbance). In reality, these queues can have a negative impact to traffic conditions upstream of the protected network that is not modelled. In this work an adaptive optimization scheme for perimeter control of heterogeneous transportation networks is developed and the aforementioned boundary control limitation is dropped. A nonlinear model is introduced that describes the evolution of the multi-region system over time, assuming the existence of well-defined MFDs. Multiple linear approximations of the model (for different set-points) are used for designing optimal multivariable integral feedback regulators. Since the resulting regulators are derived from approximations of the nonlinear dynamics, they are further enhanced in real-time with online learning/adaptive optimization, according to performance measurements. An iterative data-driven technique is integrated with the model-based design and its objective is to optimize the gain matrices and set-points of the multivariable perimeter controller based on real-time observations. The efficiency of the derived multi-boundary control scheme is tested in microsimulation for a large urban network with more than 1500 roads that is partitioned in multiple regions. The proposed control scheme is demonstrated to achieve a better distribution of congestion (by creating "artificial" inter-regional queues), thus preventing the network degradation and improving total delay and outflow. (C) 2016 Elsevier Ltd. All rights reserved.