Background: Environmental research on multifactorial health outcomes calls for exposome approaches able to assess the joint effect of multiple exposures. Objective: Our aim was to identify profiles of exposure to lifestyle/environmental factors associated with lung function in adults with asthma using a cluster-based approach. Methods: We used data from 599 adults of the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) (mean age 39.0 years, 52% men) who ever had asthma. Exposures to 53 lifestyle/environmental factors were assessed by questionnaires or geographic information systems-based models. A two-step approach was developed: 1) exposome dimension reduction by selecting factors showing association with forced expiratory volume in 1 s (FEV1) (p < 0.20) in an exposome-wide association study (ExWAS), 2) clustering analysis using the supervised Bayesian Profile Regression (sBPR) to group individuals according to FEV1 level and to their profile of exposure to a reduced set of uncorrelated exposures (each paired correlation<0.70) identified in step 1. Results: The ExWAS identified 21 factors showing suggestive association with FEV1 (none significant when controlling for multiple tests). The sBPR conducted on 15 uncorrelated exposures identified in step 1, revealed 3 clusters composed of 30, 115 and 454 individuals with a mean ± SD FEV1(%pred) of 79% ± 21, 90% ± 19 and 93% ± 16, respectively. Cluster 1 was composed of individuals with heavy smoking, poor diet, higher outdoor humidity and proximity to traffic, while cluster 2 and 3 included individuals with moderate/low levels of exposure to these factors. Discussion: This exposome study identified a specific profile of joint lifestyle and environmental factors, associated with a low FEV1 in adults with asthma. None of the exposures revealed significant association when considered independently.