Ultrafiltration and nanofiltration can be very useful technologies to fractionate the different protein fractions obtained after hydrolysis of fish by-products. Simple empirical transport equations derived from experimental data were obtained and a process simulation model was developed and employed for the identification of the optimal design and operation conditions to maximize the product purity or the process yield. More complex scenario appeared when other objectives were added to the optimization problem, including economic considerations, such as the total costs of the process, or environmental considerations, such as the total freshwater consumption by the system. Limitations to the total costs implied reduced membrane area in the UF stages and, consequently, lower process yields. Freshwater consumption could be reduced without worsening product purity or process yield, but limits should be imposed in order to avoid excessive protein contents that would cause problems related to membrane clogging.