Electronic noses (e-noses) are devices based on combining different gas sensors’ responses to a given sample for identifying specific odor fingerprints. In recent years, this technology has been considered a promising novel tool in several fields of application, but several issues still hamper its widespread use. This review paper describes how some physical confounding factors, such as temperature, humidity, and gas flow, in terms of flow direction and flow rate, can drastically influence gas sensors’ responses and, consequently, e-nose results. Among the software and hardware approaches adopted to address such issues, different hardware compensation strategies proposed in the literature were critically analyzed. Solutions related to e-nose sensors’ modification, design and readout, sampling system and/or chamber geometry design were investigated. A trade-off between the loss of volatile compounds of interest, the decrease of sensors’ sensitivity, and the lack of fast responses need to be pointed out. The existing body of knowledge suggests that the e-nose design needs to be highly tailored to the target application to exploit the technology potentialities fully and highlights the need for further studies comparing the several solutions proposed as a starting point for the application-driven design of e-nose-based systems.