Herein, we report a unique method for design and development of carboxyl enriched dendritic CuS nanostructures (CuS NSs) for photoacoustic image guided chemo-photothermal therapy. The dendritic network was grown on the surface of CuS nanoparticles via layer-by-layer assembly of amino acid. XRD and TEM studies established the formation of crystalline well-spherical nanosized hexagonal covellite (CuS) phase. The successful growth of dendritic structure was apparent from the rise in surface charge, hydrodynamic diameter and characteristic vibrational band intensity of peptide bonds. The developed different generations of dendritic CuS NSs (D0-CuS NSs, D1-CuS NSs, D2-CuS NSs and D3-CuS NSs) displayed wide-ranging absorption band in near infrared (NIR) zone and exhibited good photothermal heating efficacy upon irradiation of 980 nm laser light. From in-vitro cellular studies, it has been found that the NIR irradiation effectively enhanced the photothermal toxicity of D3-CuS NSs towards cancer cells. Moreover, these negatively charged water-dispersible D3-CuS NSs were conjugated with positively charged anticancer drug, doxorubicin hydrochloride (DOX) through electrostatic interaction. The DOX loaded D3-CuS NSs (DOX@D3-CuS NSs) revealed pH dependent drug release behaviour and their considerable uptake in breast cancer cells (MCF-7). Further, DOX@D3-CuS NSs exhibited a much higher toxicity towards cancer cells upon NIR light over individual counterparts suggesting their strong ability for chemo-photothermal therapy. Moreover, these biocompatible CuS NSs have shown excellent concentration dependent photoacoustic properties at pulse laser excitation (850 nm) and thus, they can be found potential application in chemo-photothermal therapy.