Metastasis is a main cause of cancer-related death, and a deeper understanding of the metastatic process will inform more targeted and mechanistic approaches that can abrogate challenges in treatment efficacy and toxicity. Several steps throughout the metastatic cascade, from angiogenesis to secondary tumor formation, offer specific vulnerabilities to therapies that can lead to the decline or cessation of metastatic progression. A deeper understanding of the metastatic cascade also allows combination systemic therapies to be used synergistically. In this review, we describe current treatment modalities in the context of multiple steps of the metastatic cascade. We highlight their mechanisms and present their efficacy across multiple cancers. This work also presents targets within the metastatic cascade in need of more research that can advance the landscape of treatments and lead to the goal of metastatic cancer remission.