Abstract: Implantable depots for delivering therapeutic agents and associated systems and methods are provided. In some embodiments, an implantable depot for treating pain in a subject after a surgical procedure includes a therapeutic region having a first polymer and an analgesic agent, a first control region including a second polymer, and a second control region including a third polymer. The first and second control regions can cover first and second surfaces of the therapeutic region to inhibit release of the analgesic agent therefrom. The depot can include one or more holes extending through the first and second control regions and the therapeutic region to form one or more exposed portions. When implanted in the subject, the implantable depot can release the analgesic agent from a lateral surface of the therapeutic region between the first and second surfaces, and from the exposed portions of the therapeutic region.