Animals and humans are exposed to various residues that can have a detrimental impact on health, including carcinogenic potential, endocrine disruption, or fatal toxicity. The toxic burden can be evaluated in several biological samples, with serum being one of the preferred and most convenient options. In this study, we have applied and validated a method for detecting several hundred toxins in serum samples. This technique involved a single-step QuEChERS (quick, easy, cheap, effective, rugged, and safe) extraction followed by analysis using gas and liquid chromatography coupled with mass spectrometry. With this methodology, we could detect and quantify up to 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticides, using just 250 µL of serum. Among them, 92% could be measured at concentrations below 1.25 ng/mL, making it ideal for biomonitoring. We applied this method to samples collected from camels (n= 40) and humans (n= 25). We detected naproxen, ketoprofen, paracetamol, levamisole, and some POPs in these samples. This study validated the ability to simultaneously detect a broad range of compounds in small volumes of serum.