Abstract: Disclosed herein are methods for using therapeutic compounds, for example BH3 mimetics such as MCL1 inhibitors, to treat patients that may have failed to respond to targeted or immunotherapy treatments. In several embodiments, methods for treating such patients include combining MCL1 inhibitors with immunotherapies to enhance immunotherapy treatment. For example, the combination of MCL1 inhibitors with immunotherapies is used to treat cancer, such as melanoma. In some embodiments, MCL1 inhibitory compounds and therapies may be useful in treating tissues or tumors having one or more MDSC cell expressing high levels of MCL1. In some embodiments, MCL1 and BCL2 inhibitory compounds and therapies comprising same may be used to treat one or more melanomas, for example cutaneous melanoma, melanoma subtypes selected from uveal, acral, and mucosal. In some embodiments, MCL1 inhibitory compounds and therapies comprising same may be used to treat one or more melanomas, for example uveal melanoma.