Monoclonal antibodies (mAbs) and fusion proteins with an Fc portion of immunoglobulin G (IgG) are emblematic of the remarkable expansion of biopharmaceuticals. Despite their biological origin, these products display an interindividual variability in their efficacy and/or side effects, which must be taken into consideration. Biological monitoring allowing for adapted prescription and dose adjustments may lead to therapeutic optimization and limitation of the high costs of these drugs. Herein, we review the biological theranostic of mAbs and Fc fusion proteins, including pre-treatment analyses, monitoring of efficacy, therapeutic drug monitoring, and monitoring of side effects. Supported by concrete evidence, a specific interest is given to individualised therapeutic monitoring that combines intention to treat, biomarkers of efficacy and adaptation of serum concentrations.