Currently 40% of EU's final energy consumption is attributed to buildings. Achieving the EU's climate targets would entail improved strategies in designing nearly Zero Energy Buildings. This research aimed to create an integrated decision-making strategy in designing ZEBs with the use of multi-objective optimization of building design and construction parameters for minimizing energy demand, while maximizing energy production and adaptive thermal comfort. Goal is to define which parameters have the highest impact and potential for further optimization and to offer an alternative to current stepped strategies such as the New Stepped Strategy. The proposed integrated approach is applied on a typical high-rise office building in Greece. Energy simulations with DesignBuilder are used as benchmark for the optimization run with EnergyPlus through Rhino and Grasshopper software via the plug-ins Honeybee and Ladybug, coupled with modeFRONTIER. For the first optimization round, the investigated parameters are: window-to-wall ratio, wall U-value, glazing construction U-value, glazing g-value, air-tightness of the facade, cooling set-point of the mechanical cooling system and PV facade surface area. For the second round, the parameters of window-to-wall ratio, shading area and PV surface area are adapted for four facade orientations. The optimizations resulted in a building with an annual final energy reduction of 33%.