In this paper, a new formulation for the retrofit of heat exchanger networks considering process modifications is presented. The method accounts for the interactions between the process conditions and the heat integration options to provide an optimal structure for a redesigned heat exchanger network. The formulation is based on a superstructure that considers explicitly the plant layout and the piping arrangement, which yields a mixed-integer nonlinear programming model. The model presented here includes the treatment of isothermal process streams that exchange their latent heats, in addition to the streams commonly considered with sensible heat loads. The objective function consists of maximizing the total annual profit for the retrofit process, which includes the income from products sales and the expenses due to raw materials, capital cost for new units, utility costs, and the piping modification costs. The results for the cases of study show that significant improvement in the process profitability can be obtained with the simultaneous approach presented in this work for process retrofit with respect to the sole consideration of the heat exchanger networks.