It is significant to study and improve the flexibility of chemical plants. The flexibility defined as the capability to operate this plant over a range of conditions under external disturbances or inherent uncertainty while satisfying performance specifications by convenient control variables adjustment. The target of this work is to introduce a new approach for designing optimal flexible Heat Exchanger Network (HEN) in a similar fashion of multi-period design depending on similar period durations of worst operating conditions. These worst conditions lie within the uncertainty range in terms of extreme heat load requirements to decrease number of exhaustive iteration and enhance flexibility index from the first design step. This contribution work presents a combined systematic procedure for optimum flexible HEN design based on several mathematical models using linear Interactive and Discrete Optimizer (LINDO) software and Heat Integration Network Targeting (HINT) software. Also provide with comparison and evaluation of existing methods with case study. This presented work resulted in optimum flexible HEN with controllable structure without losing stream targets while keep working at minimum energy consumption levels and achieved minimum Total Annual Costs (TACs) rather than two works in comparison.