This paper presents a new approach for mitigating fouling in existing heat exchanger networks. It is based on the recognition that operating variables, such as wall temperature and flow velocity, may have a significant effect on fouling deposition rate. The approach combines the optimization of operating conditions with the optimal management of cleaning actions in a comprehensive mitigation strategy. The application of the method is demonstrated with a case study of a refinery crude oil preheat train. Compared with the existing strategy to mitigate fouling by managing cleaning, the proposed approach leads to higher energy savings, lower operational costs and fewer disturbances to the background process.