This paper presents a flexible HEN (heat exchanger network) synthesis methodology for designing a multiperiod HEN with streams involving phase changes. The methodology is based on an MINLP (mixed integer nonlinear programming) model, identification of critical points, and flexibility index analysis considering phase changes. A nominal multiperiod HEN topology is constructed in the first step. Then each process operating condition’s critical points and flexibility index are calculated to verify the feasibility of the designed HEN under multiple operating conditions. To verify the validity of the method, the proposed methodology will be applied to a case study on an ammonia synthesis process heat transfer network design based on renewable energy. The results show that the method can obtain a flexible heat transfer network that is cost-effective and adaptable to multi-condition production for green ammonia synthesis.