Monte Carlo (MC) simulations have become important in advancing nanoparticle (NP)-based applications for cancer imaging and therapy. This review explores the critical role of MC simulations in modeling complex biological interactions, optimizing NP designs, and enhancing the precision of therapeutic and diagnostic strategies. Key findings highlight the ability of MC simulations to predict NP bio-distribution, radiation dosimetry, and treatment efficacy, providing a robust framework for addressing the stochastic nature of biological systems. Despite their contributions, MC simulations face challenges such as modeling biological complexity, computational demands, and the scarcity of reliable nanoscale data. However, emerging technologies, including hybrid modeling approaches, high-performance computing, and quantum simulation, are poised to overcome these limitations. Furthermore, novel advancements such as FLASH radiotherapy, multifunctional NPs, and patient-specific data integration are expanding the capabilities and clinical relevance of MC simulations. This topical review underscores the transformative potential of MC simulations in bridging fundamental research and clinical translation. By facilitating personalized nanomedicine and streamlining regulatory and clinical trial processes, MC simulations offer a pathway toward more effective, tailored, and accessible cancer treatments. The continued evolution of simulation techniques, driven by interdisciplinary collaboration and technological innovation, ensures that MC simulations will remain at the forefront of nanomedicine's progress.