Metastasis, the hallmark of cancer, is a complex process involving the dissemination of cancer cells from the primary tumor to distant sites, leading to the formation of secondary tumors. Despite its significance in cancer mortality, the molecular mechanisms underlying metastasis remain poorly understood. Recent research has uncovered key molecular principles that govern the metastatic process, including the role of genetic and epigenetic modifications, the interaction of cancer cells with the tumor microenvironment, and the influence of various signaling pathways. The metastatic cascade involves several steps, including invasion, intravasation, circulation, extravasation, and colonization. Epithelial-mesenchymal transition (EMT) is a critical process that enables cancer cells to acquire migratory and invasive properties. EMT is a dynamic process that can be influenced by various factors, including growth factors, signaling pathways, and environmental cues. The transition between epithelial and mesenchymal phenotypes is a spectrum, not a binary choice, and is regulated by multiple factors. EMT is not only important for the initial steps of metastasis but also contributes to chemoresistance in cancer cells. The genetic profile of metastatic cells is diverse, with different genes and mutations playing roles in metastatic progression and drug resistance. Metastatic cancer cells depend on specific metabolic pathways, such as those involving monocarboxylate transporter 1 (MCT1), to survive and proliferate. Hypoxia, a common feature of solid tumors, also plays a significant role in promoting metastasis by activating pathways such as HIF-1α and HIF-2α. The premetastatic niche (PMN) is a specialized microenvironment that is selectively primed by the primary tumor before metastasis occurs. This niche is influenced by various factors, including exosomes, which can transfer metastatic properties between cells. The PMN provides a favorable environment for metastatic cells to survive, proliferate, and colonize. Exosomes, which are extracellular vesicles released by cancer cells, play a crucial role in metastasis by transferring genetic material, signaling molecules, and other factors that promote cancer progression. Exosomes can also influence the tumor microenvironment by remodeling the extracellular matrix (ECM) and promoting angiogenesis. The interaction of cancer cells with the immune system is also critical in metastasis. Immune cells, such as neutrophils and macrophages, can either promote or inhibit metastasis depending on the context. The immune microenvironment around the tumor can influence the metastatic potential of cancer cells. In addition, the circadian clock and the microbiome have been shown to influence cancer progression and metastasis. Disruptions in circadian rhythms can lead to changes in gene expression and metabolic pathways that promote cancer growth. The tumor microbiome, which consists of bacteria present within the tumor, can also influence cancer progression by altering the tumor microenvironment and affecting the response to therapy.Metastasis, the hallmark of cancer, is a complex process involving the dissemination of cancer cells from the primary tumor to distant sites, leading to the formation of secondary tumors. Despite its significance in cancer mortality, the molecular mechanisms underlying metastasis remain poorly understood. Recent research has uncovered key molecular principles that govern the metastatic process, including the role of genetic and epigenetic modifications, the interaction of cancer cells with the tumor microenvironment, and the influence of various signaling pathways. The metastatic cascade involves several steps, including invasion, intravasation, circulation, extravasation, and colonization. Epithelial-mesenchymal transition (EMT) is a critical process that enables cancer cells to acquire migratory and invasive properties. EMT is a dynamic process that can be influenced by various factors, including growth factors, signaling pathways, and environmental cues. The transition between epithelial and mesenchymal phenotypes is a spectrum, not a binary choice, and is regulated by multiple factors. EMT is not only important for the initial steps of metastasis but also contributes to chemoresistance in cancer cells. The genetic profile of metastatic cells is diverse, with different genes and mutations playing roles in metastatic progression and drug resistance. Metastatic cancer cells depend on specific metabolic pathways, such as those involving monocarboxylate transporter 1 (MCT1), to survive and proliferate. Hypoxia, a common feature of solid tumors, also plays a significant role in promoting metastasis by activating pathways such as HIF-1α and HIF-2α. The premetastatic niche (PMN) is a specialized microenvironment that is selectively primed by the primary tumor before metastasis occurs. This niche is influenced by various factors, including exosomes, which can transfer metastatic properties between cells. The PMN provides a favorable environment for metastatic cells to survive, proliferate, and colonize. Exosomes, which are extracellular vesicles released by cancer cells, play a crucial role in metastasis by transferring genetic material, signaling molecules, and other factors that promote cancer progression. Exosomes can also influence the tumor microenvironment by remodeling the extracellular matrix (ECM) and promoting angiogenesis. The interaction of cancer cells with the immune system is also critical in metastasis. Immune cells, such as neutrophils and macrophages, can either promote or inhibit metastasis depending on the context. The immune microenvironment around the tumor can influence the metastatic potential of cancer cells. In addition, the circadian clock and the microbiome have been shown to influence cancer progression and metastasis. Disruptions in circadian rhythms can lead to changes in gene expression and metabolic pathways that promote cancer growth. The tumor microbiome, which consists of bacteria present within the tumor, can also influence cancer progression by altering the tumor microenvironment and affecting the response to therapy.