Monitored natural attenuation (MNA) and engineered bioremediation have been recognized as effective and cost-efficient in situ treatments to mitigate 1,4-dioxane (dioxane) contamination. Dioxane metabolism can be initiated by two catabolic enzymes, propane monooxygenase (PRM) and tetrahydrofuran monooxygenase (THM), belonging to the group-6 and 5 of soluble di-iron monooxygenase family, respectively. In this study, we comprehensively compared catalytic behaviors of PRM and THM when individually expressed in the heterologous host, Mycobacterium smegmatis mc2-155. Kinetic results revealed a half-saturation coefficient (Km) of 53.0 ± 13.1 mg/L for PRM, nearly 4 times lower than that of THM (235.8 ± 61.6 mg/L), suggesting that PRM has a higher affinity to dioxane. Exposure with three common co-contaminants (1,1-dichloroethene, trichloroethene, and 1,1,1-trichloroethane) demonstrated that PRM was also more resistant to their inhibition than THM. Thus, dioxane degraders expressing PRM may be more physiologically and ecologically advantageous than those with THM at impacted sites, where dioxane concentration is relatively low (e.g., 250 to 1000 μg/L) with co-occurrence of chlorinated solvents (e.g., 0.5 to 8 mg/L), underscoring the need of surveying both PRM and THM-encoding genes for MNA potential assessment. PRM is also highly versatile, which breaks down cyclic molecules (dioxane, tetrahydrofuran, and cyclohexane), as well as chlorinated and aromatic pollutants, including vinyl chloride, 1,2-dichloroethane, benzene, and toluene. This is the first report regarding the ability of PRM to degrade a variety of short-chain alkanes and ethene in addition to dioxane, unraveling its pivotal role in aerobic biostimulation that utilizes propane, isobutane, or other gaseous alkanes/alkenes (e.g., ethane, butane, and ethene) to select and fuel indigenous microorganisms to tackle the commingled contamination of dioxane and chlorinated compounds.