Nowadays, laser and nanotechnology have drawn more attention in the field of noninvasive cancer treatment with precise ablation of tumor preserving the surrounding healthy tissue. Besides, the assessment of viscoelastic deformation within the tissue can estimate the thermally induced nociceptive pain during laser therapy. This study deals with a laser-assisted in vitro thermal analysis on vascular tissue phantom doped with gold nanorods along with a comparative study with numerical results. The prediction of tissue thermomechanical response under laser heating also has been made. Both Pennes and dual-phase-lag bioheat equations coupled with equilibrium equations are solved using comsolmultiphysics (Bangalore, India). The aim is to create a comparative study between intratumoral (IT) and intravenous (IV) infusion schemes of nanoparticles in terms of thermal and mechanical behavior. The in vitro heating of tissue phantom with IT scheme provides more control over the spreading of necrotic temperature in terms of precise damage of the targeted area, preserving the surrounding nontargeted area. Predicted results show a reduced overall thermal deformation of the nanoparticle doped tissue model with the IT scheme depicting a stiffer thermoelastic response comparing the model doped with the IV scheme. The simultaneous heating and cooling shows a viscoelastic nature of biotissue. However, under cyclic heating and cooling of the tissue model embedded in a large blood vessel (LBV) depicts a smaller sized stress–strain hysteresis loop. Nevertheless, the present findings can help to understand the thermo-mechanical behavior of tissue during clinical photothermal therapy.