Background: This review re-evaluates therapeutic drug monitoring (TDM) by comparing the current analytical and subsequent clinical interpretation capabilities of hospital or community medical laboratories with the emerging potential of point-of-care (POC) devices, which could become increasingly utilized in hospital wards, day-hospital units, and outpatient clinic settings. Methods: A narrative review was conducted to identify publications that best illustrate the current trends in the development of POC TDM. Results: The latest scientific and technical literature indicates that POC devices for determining drug concentrations in clinical samples are approaching the market. Several technologies are now available to develop portable sensors capable of rapidly returning concentration measurements. Interfacing these methods with artificial intelligence-based pattern recognition may enhance the identification and quantification of drugs. However, once the drug concentration is accurately measured using a portable device, dosage adjustments require consideration of the drug's pharmacokinetics and the patient's characteristics. This is accounted for in the mathematical approaches underlying model-informed precision dosing, which consider inter- and intra-individual variability and provide recommendations for treatment adjustments. These complexities necessitate the use of digital technologies, including graphical interfaces, machine learning approaches, and secure connectivity, to enhance the application of TDM in clinical practice. Conclusions: Promising emerging technologies have considerable potential to expand TDM to cover a wide range of drugs, making precision medicine accessible to many patients.