Introduction Cancer imposes a high economic burden with medical care and medication costs. We evaluate the costs, the use of resources, the administration time, and the patient preferences associated with the use of biotechnological drugs in SC and IV presentations.Methodology A systematic literature search was conducted in PubMed, Embase, and seven additional databases. The search was carried out in September 2021 and included only studies directly comparing SC and IV presentations. Evidence was synthesized narratively.Results 34 references were included, which only analyzed bortezomib, daratumumab, rituximab, and trastuzumab. Reduction in preparation costs of SC compared to IV presentations ranged from 6.6% to 50.1%, and in administration costs from 4.5% to 95.3%. SC administration of rituximab and trastuzumab resulted in less productivity loss. More than 68% of patients reported greater satisfaction with the SC route. A reduction of time in the infusion chair, lower costs of resources for preparation, and health personnel for the administration process were identified with SC administration.Conclusions The use of SC daratumumab, rituximab, and trastuzumab in patients with cancer reduces direct and indirect costs and adverse events compared to IV use. Patients prefer the SC administration, perceiving more comfort, and less pain at the administration site.