The process industries are characterized by a large number of continuously operating plants, for which optimal operation is of economic and ecological importance. Many industrial systems can be regarded as an arrangement of several subsystems, where outputs of certain subsystems are inputs to others. This gives rise to the notion of interconnected systems. Plant optimality is difficult to achieve when the model used in optimization is inaccurate or in the presence of process disturbances. However, in the presence of plant-model mismatch, optimal operation can be enforced via specific real-time optimization methods. Specifically, this thesis considers so-called Modifier-Adaptation schemes which achieve plant optimality by direct incorporation of process measurements in the form of first-order corrections. As a first contribution, this thesis proposes a novel problem formulation for modifier adaptation. Specifically, it is focused on plants consisting of multiple interconnected subsystems that allows problem decomposition and application of distributed optimization strategies. The underlying key idea is the use of measurements and global plant gradients in place of an interconnection model. As a second contribution, this thesis investigates modifier adaptation for interconnected systems relying on local gradients by using an interconnection model. We show that the use of local information in terms of model, gradients and measurements is sufficient to optimize the steady-state performance of the plant. Finally, we propose a distributed modifier-adaptation algorithm that, besides the interconnection model and local gradients, employs a coordinator. For this scheme, we prove feasible-side convergence to the plant optimum, where a coordinator ensures that the local optimal inputs computed for each subsystem are consistent with the interconnection model. The experimental effort necessary to estimate the plant gradients increases with the number of plant inputs and may become intractable and sometimes not feasible or reliable for large-scale interconnected systems. The proposed approaches that use the interconnection model and local gradients overcome this problem. As an application case study of industrial relevance, this thesis investigates the problem of optimal load-sharing for serial and parallel gas compressors. The aim of load-sharing optimization is operating compressor units in an energy-efficient way, while at the same time satisfying varying load demands. We show how the structure of both the parallel and serial compressor configurations can be exploited in the design of tailored modifier adaptation algorithms based on efficient estimation of local gradients. Our findings show that the complexity of this estimation is independent of the number of compressors. In addition, we discuss gradient estimation for the case where the compressors are operating close to the surge conditions, which induces discontinuities in the problem.