Humans are at risk from exposure to extremes in their environment, yet there is no consistent way to fully quantify and understand the risk when considering more than just meteorological variables. An outdoor 'bio-comfort' threshold is defined for Melbourne, Australia using a combination of heat stress, air particulate concentration and grass pollen count, where comfortable conditions imply an ideal range of temperature, humidity and wind speed, acceptable levels of air particulates and a low pollen count. This is a new approach to defining the comfort of human populations. While other works have looked into the separate impacts of different variables, this is the first time that a unified bio-comfort threshold is suggested. Composite maps of surface pressure are used to illustrate the genesis and evolution of the atmospheric structures conducive to an uncomfortable day. When there is an uncomfortable day due to heat stress conditions in Melbourne, there is a high pressure anomaly to the east bringing warm air from the northern interior of Australia. This anomaly is part of a slow moving blocking high originating over the Indian Ocean. Uncomfortable days due to high particulate levels have an approaching cold front. However, for air particulate cases during the cold season there are stable atmospheric conditions enhanced by a blocking high emanating from Australia and linking with the Antarctic continent. Finally, when grass pollen levels are high, there are northerly winds carrying the pollen from rural grass lands to Melbourne, due to a stationary trough of low pressure inland. Analysis into days with multiple types of stress revealed that the atmospheric signals associated with each type of discomfort are present regardless of whether the day is uncomfortable due to one or multiple variables. Therefore, these bio-comfort results are significant because they offer a degree of predictability for future uncomfortable days in Melbourne.