The complexity and dynamics of human diseases are driven by the interactions between internal molecular activities and external environmental exposures. Although advances in omics technology have dramatically broadened the understanding of internal molecular and cellular mechanisms, understanding of the external environmental exposures, especially at the personal level, is still rudimentary in comparison. This is largely owing to our limited ability to efficiently collect the personal environmental exposome (PEE) and extract the nucleic acids and chemicals from PEE. Here we describe a protocol that integrates hardware and experimental pipelines to collect and decode biotic and abiotic external exposome at the individual level. The described protocol has several advantages over conventional approaches, such as exposome monitoring at the personal level, decontamination steps to increase sensitivity and simultaneous capture and high-throughput profiling of biotic and abiotic exposures. The protocol takes ~18 h of bench time over 2-3 d to prepare samples for high-throughput profiling and up to a couple of weeks of instrumental time to analyze, depending on the number of samples. Hundreds to thousands of species and organic compounds could be detected in the airborne particulate samples using this protocol. The composition and complexity of the biotic and abiotic substances are heavily influenced by the sampling spatiotemporal factors. Basic skillsets in molecular biology and analytical chemistry are required to carry out this protocol. This protocol could be modified to decode biotic and abiotic substances in other types of low or ultra-low input samples.