This paper addresses an integral optimization of fermentation processes. The behavior of the fermentors is described by a set of algebraic and differential equations written as finite-difference equations in an equation-oriented environment. Unconventional constraints related to the number of batch items and connections among them, detailed kinetic models and operating costs corresponding to inoculum, and different available substrates are included in the model. The optimal number of units to be used in the process, their optimal operation policy (i.e., connected in series or in parallel working out of phase), as well as the optimal volume and operation of each unit, are determined simultaneously. The model is formulated as a sequence of nonlinear programming (NLP) problems.