Protein-based nanoparticles (PNPs) in tumor therapy hold immense potential, combining targeted delivery, minimal toxicity, and customizable properties, thus paving the way for innovative approaches to cancer treatment. Understanding the various methods available for their production is crucial for researchers and scientists aiming to harness these nanoparticles for diverse applications, including tumor therapy, drug delivery, imaging, and tissue engineering. This review delves into the existing techniques for producing PNPs and PNP/drug complexes, while also exploring alternative novel approaches. The methods outlined in this study were divided into three key categories based on their shared procedural steps: solubility change, solvent substitution, and thin flow methods. This classification simplifies the understanding of the underlying mechanisms by offering a clear framework, providing several advantages over other categorizations. The review discusses the principles underlying each method, highlighting the factors influencing the nanoparticle size, morphology, stability, and functionality. It also addresses the challenges and considerations associated with each method, including the scalability, reproducibility, and biocompatibility. Future perspectives and emerging trends in PNPs' production are discussed, emphasizing the potential for innovative strategies to overcome current limitations, which will propel the field forward for biomedical and therapeutic applications.