The use of plasmonic gold nanoparticles (AuNP) that have been actively targeted to a specific tumour region is a highly active area of research for both drug delivery and hypothermia applications. One application is providing in situ cavitation nuclei for enhancing high intensity focused ultrasound (HIFU) ablation. When the nanoparticles are simultaneously exposed to HIFU and pulsed laser illumination, microscopic vapour bubbles form providing a controllable way to nucleate cavitation. Using an EGFR-expressing head and neck xenograft model, the biodistribution of targeted and untargeted AuNPs were examined using multispectral, whole body photoacoustic imaging, and inductively coupled plasma mass spectrometry (ICP-MS) analysis following systemic or intratumoral injections. Systemic delivery showed negligible concentration of AuNRs in the tumour; however, intratumoral injection increased its concentration, but remained in the tumour at high concentration for the first 48hrs. Evaluation of ablation performance was undertaken using the same tumour model. An intratumoural injection of untargeted particles, with single 10 s continuous wave HIFU exposures for peak positive/negative pressures of 2.4/2.0 MPa, with simultaneous illumination of 1064 nm pulsed laser light with a surface energy density of 70 mJ/cm2. Post treatment tumour volume was monitored using high frequency ultrasound imaging and calliper measurements, to evaluate exposure efficacy.