Despite the clear method capability towards a more sensitive and comprehensive analysis combining metabolomics and exposomics as well as targeted and untargeted in a single run, the method is not out of its limitations. Depending on the number of compounds, optimizing chromatographic separation, collision energy and declustering potential and total cycle time is time-intensive, especially for a relatively large number of compounds as described herein. We also acknowledge the lack of labeled internal standards for absolute quantification. Despite adding such compounds would lead to a more accurate calculation of the concentrations, it should be considered that additional MRM transitions would be required, further elongating total cycle time. Regarding the untargeted data, there is still the need to evaluate the influence (if any) of different SWATH accumulation times in terms of signal intensity, quality of deconvoluted spectra and, ultimately, in the total number of annotated compounds. Moreover, total accumulation times (and consequently, cycle times) may still be fine-tuned. One example is the MRM accumulation time, which can be set as compound-dependent rather than as a unique value for all, depending on overlapping transitions and total cycle time.