Background and Objective: The application ofnanotechnology for laser thermal-based killing of abnormal cells (e.g. cancer cells) targeted with absorbing nanoparticles (e.g. gold solid nanospheres, nanoshells, or rod) is becoming an extensive area of research. We develop an approach to enhance the efficiency of selective nanophotothermolysis of cancer cells through laser-induced synergistic effects around gold nanoparticles aggregated in nanoclusters on cell membrane.Study Design/Materials and Methods: A concept of selective target damage by laser-induced synergistic interaction of optical, thermal, and acoustic fields around clustered nanoparticles is presented with focus on overlapping bubbles from nanoparticles aggregated on cell's membrane. The experimental verification of this concept in vitro was performed by the use a tunable laser pulses (420-570 nm, 8-12 ns, 0.1-300 iJ, laser flux of 0.1-10 JIcm2) for irradiation of MDA-MB-23 1 breast cancer cells targeted with primary antibodies to which selectively 40-nm gold nanoparticles were attached by the means of secondary antibodies. The photothermal, electron and atomic force microscopes in combination with viability test (Annexin -V-Propidium iodide) were employed to study the nanoparticle's spatial organization, the dynamics of microbubble formations around the particle's clusters, and cells damage.Results: An aggregation of nanoparticles on cell membrane was observed with simultaneous increase bubble formation phenomena, and red-shifted absorption due to plasmon-plasmon resonances into nanoclusters. It led to a significant enhancement, at least two orders of magnitude, of the efficiency of selectively killing cancer cells with nanosecond laser pulses.Conclusion: Described approach allows using relatively small nanoparticles which would be easier delivery to target site with further creation of nanoclusters with larger sizes which provide more profound thermal and related phenomena leading to more efficient laser killing of cancer cells. This nanocluster model might be promising also for treatment or modification different targets (e.g. bacteria, virus, vascular lesions, fat, etc.) as well as the use different type energy deposition (focused ultrasound, microwave, magnetic field, etc.).