Metastasis accounts for over 90% of cancer-related mortality, representing the most advanced stage of disease progression. While primary tumors are often controlled through surgery or radiotherapy, dissemination via lymphatic, hematogenous, or trans-cavity pathways leads to poor prognosis and limited therapeutic options. Recent advances in imaging and molecular diagnostics have refined the classification of metastatic disease into oligometastatic, limited polymetastatic, and disseminated states, each a quite distinct group in terms of outcomes. Emerging evidence supports aggressive local therapies adjunct to systemic therapy, such as stereotactic ablative radiotherapy (SABR), in oligometastatic patients, offering improved progression-free and overall survival. The chapter explores the evolutionary biology of metastasis, organ-specific tropism, and the role of cellular markers in identifying primary sites in cancers of unknown origin. Radiological innovations, including CT, MRI, PET, and whole-body imaging, are highlighted as critical tools for staging and guiding treatment strategies. Collectively, these insights underscore the rationale for integrating precision diagnostics with tailored local therapeutic approaches with modern radiotherapy to improve the outcomes in selected metastatic scenarios.