<p>The skin is the body’s largest organ and is considered as a protective barrier which acts as a highly impermeable region of the human body. But in recent times, it is recognized as a specialized organ that aids in the delivery of a wide range of drug molecules into the skin (intradermal drug delivery) and across the skin into systemic circulation (transdermal drug delivery, TDD). Transdermal administration remains an active research and development area as an alternative route for long- acting drug delivery. It avoids major drawbacks of conventional oral (gastrointestinal side effects, low drug bioavailability, and need for multiple dosing) or parenteral routes (invasiveness, pain, and psychological stress and bio-hazardous waste generated from needles), thereby increasing patient appeal and compliance. The bioavailability of a drug administered transdermally can be improved by several penetration enhancement techniques, which are broadly classified into chemical and physical techniques. Application of the mentioned techniques together with efforts of various scientific and innovative companies had made TDD a multibillion-dollar market and this has led to a growing market with a steady pipeline of new transdermal products receiving regulatory approval. Out of various techniques, thermal therapeutic methods including chemical heating, laser ablation, thermoporation, radiofrequency and photothermal therapy are the top listed emerging techniques. This review article mainly discussed about these thermal ablation techniques with their available commercial products along with advantages and disadvantages. This review also presented anatomy of the skin, penetration pathways across the skin, affecting factors and different generations and mechanisms of TDD. Briefly, this article discussed basics, mechanism, challenges, and future research and development directions of thermal-based TDDS.</p> Graphical Abstract <p></p>