This study experimentally investigates the thermal–hydraulic performance of heat exchanger tubes fitted with wired twisted tapes, with particular emphasis on the effects of the hole spacing-to-width ratio (s/W) and edge margin-to-width ratio (e/W). Experiments were conducted over a Reynolds number range of 6000–20,000, and the results were compared with those of plain tubes and tubes equipped with conventional twisted tapes. The findings revealed that the incorporation of wires significantly enhanced heat transfer due to the combined action of longitudinal eddies generated by wire protrusions and swirling flow induced by the twisted tape. At identical Reynolds numbers, tubes with a smaller hole spacing (s/W = 0.16) exhibited superior heat transfer performance, achieving Nusselt number enhancements of up to 107.7% relative to plain tubes and 51.6% relative to conventional twisted tapes. Similarly, reducing the edge margin ratio intensified near-wall eddies and further disrupted the boundary layer. The friction factor was found to increase with decreasing hole spacing and edge margin, primarily due to additional flow obstructions and enhanced near-wall shear stresses. For wired twisted tapes with s/W = 0.16, the friction factor reached nearly six times that of a plain tube. Despite this penalty, the thermal performance factor (TPF) remained favorable, with values of up to 1.2, indicating that the heat transfer benefits outweighed the corresponding pressure losses.