Amino acid based poly(ester amide)s are a family of biodegradable polymers which have been designed and synthesized for various biomedical applications including tissue engineering scaffold, hydrogels, coating for cardiovascular stents, nanofibrous membrane and sutures etc. The aim for this study is to investigate the potential of poly(ester amide)s materials as nano-carriers for the delivery of multiple therapeutics including chemotherapeutics, photosensitizers and proteins, in the treatment of cancer. The amino acid based poly(ester amide)s provided the physical encapsulation of the payloads, and further impact the interactions and communication with cancer cells, comparing to the direct administration of free therapeutics. In addition, by adjusting different amino acids on poly(ester amide)s, or froming hybrid nanomaterials with other biodegradable polymers, functionalities can be introduced into the delivery systems so that “smart” delivery can be achieved. The therapeutic potency of poly(ester amide)s based delivery systems, are closely related to a series of stimuli, which includes biological cues such as enzymatic degradation, or physical cues such as light. The thesis demonstrated the potency of poly(ester amide) nano-carriers from both in vitro and in vivo characterization, and further validated their application potential to be developed as spatio-temporally controllable delivery systems.