This chapter discusses the impact of obesity on tumor progression, focusing specifically on two types of cancer linked to this condition, namely, colorectal cancer (CRC) and breast cancer (BC). The main objective is to explore the complex relationship between the tumor and its microenvironment, with a focus on the role of adipocytes and their interaction with tumor cells and other components of the tumor microenvironment (TME). Bidirectional communication between adipocytes and tumor cells in the TME is highlighted, with a focus on how this interaction influences tumor progression. Key aspects, including metabolic reprogramming, lipid mobilization (mediated by proteins such as CD36, FABP4, and FASN), cellular plasticity, and the inflammatory response, are discussed. Proteins, such as MCP-1 and leptin, play key roles in these signaling pathways. Furthermore, the importance of understanding these interactions for the development of more effective therapies is noted. This chapter highlights the importance of adipocytes as a central component of the TME from both metabolic and immunological perspectives. The potential of studying these interactions to guide the development of new cancer therapies is underlined. At the same time, the use of in vitro studies to characterize these interactions and open new avenues of research is proposed, with the aim of advancing toward innovative and more effective therapeutic approaches against cancer.