Monitoring thousands of environmental chemicals in microliter blood volumes is now possible by chemical exposomics and high-resolution mass spectrometry (HRMS). As these technologies advance toward higher throughput to support human exposome studies with millions of participants, parallel implementation of higher-frequency blood collection methods must be considered to capture the highly dynamic nature of individual exposomes. Blood microsampling devices offer a less invasive way to collect quantitative, replicate, and repeated blood samples outside the clinic, overcoming limitations of traditional venepuncture and dried blood spots. Here we critically evaluate seven popular commercial microsampling devices for their potential use in chemical exposomics by considering previous use in molecular profiling, collection volumes, compatibility with various blood fractions, and conditions for shipping, storage, and analysis. We furthermore present the first data on extractable chemical interferences leaching from six of these devices in simulated blood sampling. Nontargeted HRMS revealed greatly different chemical backgrounds between devices, with implications for method sensitivity and false-positive discovery of exogenous and endogenous molecules. The unique advantages of each microsampler should be weighed against these chemical backgrounds, and in all cases, a systematic quality control program including field and simulated collection blanks is advised for future exposome studies utilizing these emerging devices.