High mountains and cold climate in the north-west of Iran are critical factors for the design of optimized District Heating (DH) systems and energy-efficient buildings. It is essential to consider the Life Cycle Cost (LCC) that includes all costs, such as initial investment and operating costs, for designing an optimum DH system. Moreover, considering climate change for accurately predicting the required heating load is also necessary. In this research, a general optimization is carried out for the first time with the aim of a new design concept of a DH system according to a LCC, while considering all-involved parameters. This optimized design is based on various parameters such as ceiling and wall insulation thicknesses, depth of buried water and heating supply pipes, pipe insulation thickness, and boiler outlet temperature. In order to consider the future weather projection, the mentioned parameters are compared with and without climate change effects in a thirty-year period. The location selection was based on the potential of the region for such a system together with the harsh condition of the area to transport the common fossil fuel to the residential buildings. The obtained results show that insulation of walls is more thermally efficient than a roof with the same area in the selected case. In this case, polyurethane is the best material, which can cause a reduction of 59% in the heating load and, consequently, 2332 tons of CO2 emission annually. The most and the least investment payback periods are associated with the polyurethane and the glass wool insulation materials with the amounts of seven and one years. For the general optimization of the DH system, the Particle Swarm Optimization (PSO) method with a constriction coefficient was chosen. The results showed that the optimal thickness of the polyurethane layer for the thermal insulation of the building exterior walls is about 14 cm and the optimal outlet temperature of the boiler is about 95 °C. It can be also concluded that the optimal depth for the buried pipes is between 1.5 to 3 m underground. In addition, for the pipe with elastomeric insulation layer, the thickness of 2 cm is the optimal choice.