A novel handheld device for the rapid, localized cooling of skin prior to needle insertion was developed to mitigate pain and improve patient comfort during injections. The device integrates a thermoelectric cooler, an optimized heat‐sink–fan assembly, and a custom cooling interface, all governed by a feedback control system. Multilayer bioheat transfer simulations were performed to establish the thermal extraction needed to inhibit dermal nociceptor activation without damaging tissues. A surrogate‐based parametric study was then conducted to prevent design divergence and identify key geometric and operating parameters—namely fin spacing, heatsink dimensions, fan clearance, and base thickness—that most strongly influenced both temperature reduction and pressure drop. Based on simulation outcomes, two heatsink architectures (pin‐ and plate‐fin) were evaluated via finite‐element analysis and experimentally validated. Plate fins were ultimately selected for their superior thermal performance, lower airflow resistance, and reduced mass. A mesh sensitivity study confirmed the convergence of results at a dimensionless grid index of 2.2, while an algebraic yPlus turbulence model ensured accurate boundary‐layer resolution. Clinical evaluation involving 1,000 healthy adults employed a 4×5 factorial design, varying cooling temperatures (0 °𝐶𝐶 to −7 °𝐶𝐶) and application durations (0−20 𝑠𝑠). Self‐reported pain scores revealed a clear analgesic optimum at −5 °𝐶𝐶 for 15 𝑠𝑠, producing an average pain reduction exceeding 80 % compared to uncooled controls, without adverse cold‐induced discomfort. Statistical analysis via two‐way ANOVA and Tukey’s HSD confirmed the independent and interactive effects of temperature and duration on analgesic efficacy. This work demonstrates the feasibility of a TEC‐based preinjection cooling device, combining rigorous computational design, experimental validation, and large‐scale clinical testing. The methodology provides a blueprint for future medical devices aimed at nonpharmacological pain management.