The lungs are among the most frequent sites of distant dissemination of malignancy, a phenomenon driven by the organ’s unique physiological properties and complex molecular interactions. This paper provides a comprehensive review of the biological mechanisms underlying pulmonary metastasis and explores their direct implications for surgical management, specifically pulmonary metastasectomy (PM). The metastatic journey is analyzed through the lens of three evolving models of tumorigenesis: the stochastic model, the cancer stem cell model, and the cellular plasticity model. Central to this dissemination is the epithelial-mesenchymal transition (EMT), a dynamic process in which tumor cells acquire a hybrid phenotype that facilitates invasion, intravasation, and immune evasion. The lung’s susceptibility is attributed to its receipt of the entire cardiac output, its dense capillary network, and its establishment of pre-metastatic niches. These niches, modulated by inflammatory responses and extracellular matrix remodeling, create a permissive microenvironment for disseminated tumor cells (DTCs) to undergo colonization or to enter states of dormancy. Clinically, the efficacy of PM is rooted in these biological realities. The necessity for radical R0 resection and systematic lymphadenectomy is supported by routes of hematogenous and lymphatic spread. Furthermore, the debate between traditional thoracotomy and minimally invasive surgery (MIS) is framed by the biological challenge of radiologically occult nodules that may require bimanual palpation for identification. A comparative perspective on colorectal carcinoma, renal cell carcinoma, sarcomas, and germ cell tumors illustrates how histological behavior dictates surgical timing and the integration of systemic therapies. While advances in immunotherapy and molecular targeting offer hope, the heterogeneity of metastatic disease and the protective nature of the pulmonary microenvironment remain significant barriers. This review underscores that future therapeutic success necessitates a multidisciplinary approach targeting both tumor-intrinsic drivers and extrinsic niche factors. Ultimately, a deeper synthesis of metastasis biology and surgical principles is essential to refine therapeutic algorithms and improve long-term survival for patients with secondary pulmonary malignancies.