Exploring the chemical space of a given ligand aiming to modulate its ligand field strength is a versatile strategy for the fine-tuning of physical properties such as the transition temperature (T1/2) of spin-crossover (SCO) complexes. The computational study presented herein aims at systematically exploring the extent to which the ligand substituent effects can modulate T1/2 in two families of Fe(III) SCO systems with a N4O2 coordination environment and at identifying the best descriptors for fast and accurate prediction of changes in T1/2 upon ligand functionalization. B3LYP* calculations show that the attachment of substituents to β-ketoiminato fragments (L1) leads to drastic changes in T1/2, while functionalization of phenolato moieties (L2) allows for a finer degree of control over T1/2. Natural Bond Orbital (NBO) charges of the donor atoms, Hammett parameters for both para and meta-functionalization of L2, and Swain-Lupton parameters for L1 and para-functionalization of L2 have been found to be the suitable descriptors for predicting the changes in T1/2. Further analysis of the ligand-field splitting in such systems rationalizes the observed trends and shows that ligand substituents modify both the σ and π bonds between the Fe(III) center and the ligands. Thus, we provide simple yet reliable guidelines for the rational design of new SCO systems with specific values of T1/2 based on their ligand design.