Office buildings are a major contributor to energy consumption in high-density urban contexts where building high-rises is a norm. It is important to understand the parameters affecting high-rise office buildings’ energy consumption. However, previous research generally used isolated buildings as target buildings, regardless of the impact brought by the surrounding buildings. Also, there lacked a comprehensive calibration method to validate the energy baseline model. This paper aims to quantitatively analyse the energy use in high-rise office buildings by tackling these two issues and examining the impacts of various energy-saving measures (ESMs). A real-life 26-story office building in Hong Kong was selected as a base case. Multiple methods were used to calibrate the building energy model, including onsite microclimate measurement, metered data, architectural drawings and official documents, and onsite surveys. Parametric sensitivity analyses were then conducted to quantify the importance of ten selected parameters from five types of ESMs. Results indicate that fan efficiency and cooling setpoint temperature had the most significant energy-saving potential. The base case of the ESMs in use was considered as the base scenario. Two new scenarios were proposed to examine the range of total energy consumption by adopting the most and least energy-efficient ESMs, which were referred to as the “optimistic scenario” and the “pessimistic scenario”. The maximum reduction/increase in energy use is expected to be approximately 13.2%/39.3% for the optimistic/pessimistic scenario compared to the base scenario. The findings on the sensitivities and scenarios contribute to a more comprehensive understanding of the critical parameters that influence energy use in high-rise office buildings in subtropical climate. The findings also provide scenario-based design solutions for delivering low-energy office buildings.