The paper proposes a solution for two main problems related to transdermal drug delivery (TDD): “How to improve the delivery rate?” and “How to deliver large molecular weight compounds into the skin?” The solution, sonophoretic enhanced microneedles array (SEMA), is a combination between two already proven TDD methods. Enhancements are achieved due to two effects, namely mechanical (hollow microneedles) and sonophoretic (low frequency). An array of hollow microneedles breaks the stratum corneum and hydrophilic microfluidic channels within the microneedles bring the drug directly to the epidermis, allowing deeper diffusion into the dermis. A sonophoretic emitter provides energy to the fluid media and induces acoustic cavitations that facilitate diffusion of large molecular compounds into the skin by improving diffusion rates. Results of in vitro released calcein and bovine serum albumin (BSA) on pig skins are presented.