The liver is one of the most common sites for metastasis, which involves the spread from primary tumors to surrounding organs and tissues in the human body. There are a few steps in cancer expansion: invasion, inflammatory processes allowing the hepatic niche to be created, adhesions to ECM, neovascularization, and secretion of enzymes. The spread of tumor cells depends on the microenvironment created by the contribution of many biomolecules, including proteolytic enzymes, cytokines, growth factors, and cell adhesion molecules that enable tumor cells to interact with the microenvironment. Moreover, the microenvironment plays a significant role in tumor growth and expansion. The secreted enzymes help cancer cells facilitate newly formed hepatic niches and promote migration and invasion. Our study discusses pharmacological methods used to prevent liver metastasis by targeting the tumor microenvironment and cancer cell colonization in the liver. We examine randomized studies focusing on median survival duration and median overall survival in patients administered placebo compared with those treated with bevacizumab, ramucirumab, regorafenib, and ziv-aflibercept in addition to current chemotherapy. We also include research on mice and their responses to these medications, which may suppress metastasis progression. Finally, we discuss the significance of non-pharmacological methods, including surgical procedures, radiotherapy, cryotherapy, radiofrequency ablation (RFA), and transarterial embolization (TAE). In conclusion, the given methods can successfully prevent metastases to the liver and prolong the median survival duration and median overall survival in patients suffering from cancer.