: Trace minerals (TMs), both essential and toxic, are integral to human physiology, participating in enzymatic reactions, oxidative balance, immune function, and the modulation of chronic disease risk. Despite their importance, imbalances due to deficiencies or toxic exposures are widespread globally. While low-income countries often face overt deficiencies and environmental contamination, middle- and high-income populations increasingly deal with subclinical deficits and chronic toxic metal exposure. This review aims to explore the relevance of serum as a matrix for evaluating TM status across diverse clinical and epidemiological, geographic, and demographic settings. : A narrative literature review was conducted focusing on the physiological roles, health impacts, and current biomarker approaches for key essential (e.g., zinc, copper, selenium) and toxic (e.g., lead, mercury, cadmium, arsenic) trace elements. Particular emphasis was placed on studies utilizing serum analysis and on recent advances in multi-element detection using inductively coupled plasma mass spectrometry (ICP-MS). : Serum was identified as a versatile and informative matrix for TM assessment, offering advantages in terms of clinical accessibility, biomarker reliability, and capacity for the simultaneous quantification of multiple elements. For essential TMs, serum levels reflect nutritional status with reasonable accuracy. For toxic elements, detection depends on instrument sensitivity, but serum can still provide valuable exposure data. The method's scalability supports applications ranging from public health surveillance to individualized patient care. : Serum trace mineral analysis is a practical and scalable approach for nutritional assessment and exposure monitoring. Integrating it into clinical practice and public health strategies can improve the early detection of imbalances, guide interventions such as nutritional supplementation, dietary modifications, and exposure mitigation efforts. This approach also supports advanced personalized nutrition and preventive care.