Abstract Employees’ wellbeing and comfort perception demonstrated to largely influence their productivity and tolerability of slight thermal discomfort conditions in the working spaces. Their whole comfort perception indeed depends on several parameters related to physical boundary conditions but also to the adaptation capability of occupants themselves and other personal, difficult to measure, variables. According to the available standards and regulations, only physical and measurable environmental parameters must be considered to evaluate occupants’ comfort conditions. Therefore, non-measurable factors such as socio-psychological, physiological, medical ones are currently not systematically considered. The present work aims to identify possible benefits in terms of occupants’ comfort perception due to non-physical strategies aimed at improving the work-environment quality and livability. To this aim, the environmental multi-physics and multi-domain performance of a mixed industry-office building is investigated through coupled in-field microclimate monitoring and questionnaires campaigns. The experimental microclimate monitoring and survey campaign were carried out to understand (i) the realistic indoor environmental conditions in terms of physical and measurable parameters and (ii) the personal perceptions and attitudes of the occupants with respect to those same ambient parameters, including also acoustic, lighting and medical investigation. Moreover, the collected experimental data were used to determine occupants’ comfort level through the classic comfort models, to be compared to the identified role of non-physical parameters on occupants’ final perception about the indoor environment. The main results show that non-measurable factors induced by virtuous company policy to improve employees’ working environment are effectively able to positively influence their whole-comfort perception even if the majority of workers do not have the opportunity to control their working environment. In fact, the consolidated comfort theories underestimate people satisfaction, as demonstrated by more than the 80% employees, who declared to be positively influenced by the pleasant aesthetics and livability of the workplace. The year-round experimental campaign demonstrated the need to further investigate the key role of non-physical parameters for possible incorporation into whole-comfort prediction models and standards. The role of such strategies could therefore be realistically considered as energy saving opportunities since they make building occupants much more open to tolerate slight uncomfortable conditions.