The commercialization of a growing number of wearable devices has been enabled within recent years due to the availability of miniaturized sensor modalities, the development of new materials, and the scalability of flexible electronics. With the increase in resource shortages within healthcare, there is a demand to translate wearable devices from the commercial consumer stand-point to the medical field. Clinical-grade signal quality, wearability, and comfort all need to be tailored to a wearable design. Wear and comfort for user compliance and durability for longer-term use are commonly overlooked. In this study, the relationship of on-body location and material layer composition is investigated. Five non-woven medical tapes noted for longer wear time are tested over a 7-day timeframe. The impact of material properties, such as elasticity, isotropy, and hysteresis, as well as the moisture vapor transmission rate (MVTR) and adhesive thickness, are evaluated in relation to skin properties on the lower torso of 30, high-activity-level volunteers. User perception was quantified via Likert-scale questionnaires and images were obtained for the material–skin interaction. The results indicate that critical characteristics, such as MVTR and elasticity, noted for positive skin interaction in commercial products, may not translate to improved user perception and durability over time. Future work will assess new design options to manipulate material properties for improved wear and comfort.