Because the impact of the full-scale substitution of Ca2+ in brushite (CaHPO4·2H2O) with Ni2+ ions has never been systematically explored, it is the focus of this investigation, as it holds potential for use in CaxNi1−xHPO4·nH2O production. These biomaterials have many beneficial characteristics that can be modified to suit diverse applications, including bone tissue regeneration and pharmaceutics. For the present study, NaH2PO4·2H2O, Ca(NO3)2·4H2O, and Ni(NO3)2·6H2O were used in various molar concentrations to obtain the required starting solutions. Previous studies have shown that adding Ni ions in the initial solution below 20% results in the precipitation of monophasic brushite with slight changes in the crystal structure. However, this study confirms that when the Ni ions substitution increases to 20%, a mixture of phases from both brushite and hexaaquanickel(II) hydrogenphosphate monohydrate HNiP (Ni(H2O)6·HPO4·H2O) is formed. The results confirm that the full replacement (100%) of Ca ions by Ni ions results in a monophasic compound solely comprising orthorhombic HNiP nanocrystals. Therefore, a novel technique of HNiP synthesis using the precipitation method is introduced in this research work. These materials are subsequently analyzed utilizing powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The obtained results confirm that the material microstructure is controlled by the Ni/Ca ratio in the starting solution and can be modified to obtain the desired characteristics of phases and crystals.