Calcium phosphate cements (CPCs) have been extensively studied in last decades as nanostructured biomaterials for the regeneration of bone defects, both for dental and orthopedic applications. However, the precise control of their handling properties (setting time, viscosity, and injectability) still represents a remarkable challenge because a complicated adjustment of multiple correlated processing parameters is requested, including powder particle size and the chemical composition of solid and liquid components. This study proposes, for the first time, a multifactorial investigation about the effects of powder and liquid variation on the final performance of Sr-doped apatitic CPCs, based on the Design of Experiment approach. In addition, the effects of two mixing techniques, hand spatula (low-energy) and planetary shear mixing (high-energy), on viscosity and extrusion force were compared. This work aims to shed light on the various steps involved in the processing of CPCs, thus enabling a more precise and tailored design of the device, based on the clinical need.