Energy retrofitting of existing building stock has significant potential for the reduction of energy consumption and greenhouse gas emissions. Roughly half of the CO2 emissions from Czech building stock are estimated to be allocated to residential buildings. Approximately one-third of the Czech residential building stock have already been retrofitted, but retrofitting mostly takes place in large cities due to greater income. A favourable concept for the mass retrofitting of residential building stock, affordable even in low-income regions, was of interest. For a reference building, multi-criteria assessment of numerous retrofitting measures was performed. The calculation involved different building elements, materials, solutions, and energy-efficiency levels in combination with various heating systems. The assessment comprised environmental impact, represented by operational and embodied primary energy consumption and greenhouse gas emissions, and investment and operational costs using the annuity method. Analysis resulted in the identification of favourable retrofitting measures and showed that complex building retrofitting is advantageous from both a cost and an environmental point of view. The environmental burden could be decreased by approximately 10−30% even without photovoltaic installation, and costs per year could be decreased by around 40%.