Abstract: Systems, methods, and devices for treating a subject are described herein. In some embodiments, an applicator for selectively affecting a subject's subcutaneous tissue is provided. The applicator can include: a housing; a treatment cup mounted in the housing, wherein the treatment cup defines a tissue-receiving cavity and includes a temperature-controlled surface; at least one thermal device coupled to the treatment cup and configured to receive energy via a flexible connector coupled to the applicator and to cool the temperature-controlled surface; an at least one vacuum port coupled to the treatment cup and configured to provide a vacuum to draw the subject's tissue into the tissue-receiving cavity and against at least a portion of a treatment area of the temperature-controlled surface to selectively damage and/or reduce the subject's subcutaneous tissue.