Abstract: This study investigates the sources of uncertainty in determining the lead content in metronidazole pharmaceuticals using inductively coupled plasma mass spectrometry (ICP-MS). Following the 2321 method of the Pharmacopoeia of the People’s Republic of China (2020 edition), lead content was measured using ICP-MS post-microwave digestion. The study analyzed the uncertainty contributed by sample weighing, microwave digestion, preparation of standard working solutions, regression fitting of the standard curve, and repeatability of measurements to establish combined and expanded uncertainties. The findings indicate that the preparation of standard working solutions is the primary contributor to uncertainty, with a relative uncertainty of 1.44%. Other factors such as sample weighing, microwave digestion, and repeatability have a lesser impact on the overall uncertainty. For a sample weight of 0.10 g, the lead content in metronidazole tablets was found to be 0.5063 μg/g, with an expanded uncertainty of 0.01793 μg/g (k = 2).