Potentiometric ion-selective electrode (ISE) sensors are powerful electrochemical tools used in various applications in different fields, including the biological, clinical, and environmental fields, owing to their high selectivity, sensitivity, simplicity, and versatility. This review highlights recent advancements in ionophore-based polymeric ISE sensors over the past five years, with a particular focus on progress at the micro- and nanoscales. After discussing the conventional ISE configuration and its general operational principles, we explore the notable advancements in terms of the key ion-selective membrane components, such as ionophores, and other techniques combined with ISEs. These advancements have significantly improved the sensing performances and expanded the practical applications. We also examine the progress in the field of miniaturized solid-contact microelectrodes and the incorporation of novel functional materials for efficient ion-to-electron transduction. Miniaturized solid-state ISEs provide low limits of detection with reduced sample volume requirements, extended stability, and rapid response times. When combined with scanning electrochemical microscopy, ion-selective microelectrodes enable highly spatially resolved ion analyses. The integration of solid-contact ISEs into compact, portable, wearable devices has advanced the field of wearable on-body ISE sensors. Finally, we briefly introduce the development of ion-selective optode sensors as promising optical sensors based on ionophores that are particularly advantageous for cellular imaging.