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Buildings use a significant amount of primary energy and largely contribute to greenhouse gases emission. Cost optimality and cost effectiveness, including cost-optimal operation, are important for the adoption of energy efficient and environmentally friendly technologies. The long-term assessment of buildings-related greenhouse gases emission might take into account cost-optimal operation of their energy systems. This is often not the case in the literature. Long-term operation optimization problems are often of large scale and computationally intensive and time consuming. This paper formulates a bottom-up methodology relying on an efficient, but precise operation optimization approach, applicable to long-term problems and use with buildings simulations. We suggest moving-horizon short-term optimization to determine near-optimal operation modes and show that this approach, applied to flexible energy systems without seasonal storage, have satisfactory efficiency and accuracy compared with solving problem for an entire year. We also confirm it as a valuable pre-solve technique. Approach applicability and the importance of energy systems optimization are illustrated with a case study considering buildings envelope improvements and cogeneration and heat storage implementation in an urban residential settlement. EnergyPlus is used for buildings simulations while mixed integer linear programming optimization problems are constructed and solved using the custom-built software and the branch-and-cut solver Gurobi Optimizer.