Recently, the advancement of nanotechnology has had a significant impact on clinical therapeutics. Advances in biocompatible drug carriers using organic/inorganic nanoparticles have enabled safer and more efficient delivery of anti-cancer agents. In particular, nanoparticles designed and fabricated by sophisticated processes can (as drug carriers) deliver precise doses of multiple anti-cancer agents to target cancer cells, improving therapeutic efficacy and minimizing side effects. In addition, a comprehensive understanding of cancer biology, chemo-resistance, cancer relapse, and metastasis is essential for successful development of combination therapy using nanoparticles. In this review, we discuss the species of functional nanoparticles for delivery of anti-cancer agents and their potential to improve chemotherapeutic indices via combination therapy. We also discuss novel therapeutic strategies using functional nanoparticles developed through multidisciplinary collaboration for combination chemotherapy.