AbstractDermal interstitial fluid (ISF) is emerging as a rich source of biomarkers that complements conventional biofluids such as blood and urine. However, the impact of ISF sampling in clinical applications has been limited owing to the challenges associated with extraction. The implementation of microneedle‐based wearable devices that can extract dermal ISF in a pain‐free and easy‐to‐use manner has attracted growing attention in recent years. Here, a fully integrated touch‐activated wearable device based on a laser‐drilled hollow microneedle (HMN) patch for continuous sampling and sensing of dermal ISF is introduced. The developed platform can produce and maintain the required vacuum pressure (as low as ≈ −53 kPa) to collect adequate volumes of ISF (≈2 µL needle⁻¹ h⁻¹) for medical applications. The vacuum system can be activated through a one‐touch finger operation. A parametric study is performed to investigate the effect of microneedle array size, vacuum pressure, and extraction duration on collected ISF. The capability of the proposed platform for continuous health monitoring is further demonstrated by the electrochemical detection of glucose and pH levels of ISF in animal models. This HMN‐based system provides an alternative tool to the existing invasive techniques for ISF collection and sensing for medical diagnosis and treatment.