Purpose of Review <p>Metastasis, the spread of cancer cells to distant organs, is the leading cause of cancer-related deaths. It is a highly inefficient process requiring cells to adapt and survive the changing microenvironments. This review explores how metastatic cells adapt to these dynamics, driving cancer progression.</p> Recent Findings <p>Cancer stem cells (CSCs), a subpopulation of cells with self-renewal property, is crucial for survival of metastatic cells in dynamic microenvironments. Additionally, metastatic cells exhibit metabolic plasticity, enabling them to utilize diverse energy sources across different microenvironments during metastasis. Moreover, CSCs also show metabolic plasticity. Thus, implying interconnectedness of metastasis, CSCs and metabolic plasticity. Repurposing existing therapies targeting CSCs and metabolic plasticity offers potential for novel strategies to combat metastasis.</p> Summary <p>This review explores the interplay between metastasis, CSCs and metabolic plasticity in cancer progression and provides insights into current therapeutic strategies targeting these mechanisms.</p>