Dissolving microneedles (DMNs) have been used as an alternative drug delivery system to deliver therapeutics across the skin barrier in a painless manner. In this study, we propose a novel heat-melting method for the fabrication of hydrophobic poly(lactic-co-glycolic acid) (PLGA) DMNs, without the use of potentially harmful organic solvents. The drug-loaded PLGA mixture, which consisted of a middle layer of the DMN, was optimized and successfully implanted into ex vivo porcine skin. Implanted HMP-DMNs separated from the patch within 10 min, enhancing user compliance, and the encapsulated molecules were released for nearly 4 weeks thereafter. In conclusion, the geometry of HMP-DMNs was successfully optimized for safe and effective transdermal sustained drug delivery without the use of organic solvents. This study provides a strategy for the innovative utilization of PLGA as a material for transdermal drug delivery systems.