The current indoor, building envelope and energy analysis tools are in the form of stand-alone packages, where there is no direct link among them but rather simplifying assumptions are made on the indoor conditions or building envelope when designing for one. For example, indoor models attempt to predict the indoor condition with a simplified approach or no coupling with the building components, which in fact could have a moisture buffering effect. Building envelope models use predefined simple indoor environmental conditions in assessing the hygrothermal performance of a particular building component. Energy models usually ignore the moisture effect on the thermal transport and storage properties of materials. Incorrect prediction of indoor humidity condition and ignoring moisture effect in the energy calculation may lead to over or under sizing of HVAC equipments and the associated effects on building enclosure moisture performance and occupants' comfort and health. In reality, the indoor environmental conditions, more specifically, temperature and relative humidity, are unknown quantities, and have to be determined from the heat and mass balance in the zone considering the heat and mass transfer across the building enclosure, the internal heat and moisture generated by occupants and their activities, and the heat and moisture supply from mechanical systems depending on the mode of operation of the building. In this research work, a whole building hygrothermal model, which considers the building as a system and deals with the dynamic heat, air and moisture (HAM) interactions among building envelope components, indoor environment and mechanical systems, is developed. The model takes into account the three interrelated and coupled components and evaluates the indoor temperature and relative humidity, building enclosure moisture performance and energy efficiency of the building in an integrated manner on a single platform. The model along with two primary models, namely building envelope and indoor models, are benchmarked against internationally published analytical, numerical and experimental test cases. After successful benchmarking, its usefulness in practical applications are demonstrated through indoor humidity modeling of an existing building, and evaluation of the subsequent retrofit options to attain indoor humidity that is favorable to occupants' comfort and health and at the same time high energy efficiency and durable building. The whole building heat and moisture analysis that are carried out in this research work underlines the importance of an integrated design approach in designing new buildings or retrofitting existing buildings in order to attain an optimized building performance.