Process lifecycle has several stages, including process design covered in multiple stages. Process economics is a vital factor in finalizing the process design. Besides economics, inherent safety is an important concept contributing to sustainable process design generation. The inherent safety concept has been applied via equipment characteristics for individual equipment. Since a method considering inherent safety with equipment aspects and process economics has not been available, therefore, a new method has been proposed, namely sustainable process design for heat exchanger network (SPDHEN), to integrate inherent safety, equipment aspects, and process economics. SPDHEN uses indexing to identify the critical heat exchanger, which is then examined via hazard analysis for an explosion. For unacceptable hazards, inherent safety principles are engaged to generate design alternatives for which process economics is examined too. The final design would be inherently safer with the best profit margin. The proposed method has been studied for the ammonia synthesis loop. It is concluded that the explosion hazard has been reduced to a tolerable level by using inherent guide words with a marginal compromise on quantity of ammonia produced, that is, 0.32%. This method is straightforward and can be useful for process engineers to generate sustainable process designs for heat exchanger networks considering safety and process economics simultaneously.