The multifactorial nature of cancer still classifies the disease as one of the leading causes of death worldwide. Modern medical sciences are following an interdisciplinary approach that has been fueled by the nanoscale revolution of the past years. The exploitation of high-Z materials, in combination with ionizing or non-ionizing radiation, promises to overcome restrictions in medical imaging and to augment the efficacy of current therapeutic modalities. Gold nanoparticles (AuNPs) have proven their value among the scientific community in various therapeutic and diagnostic techniques. However, the high level of multiparametric demands of AuNP experiments in combination with their biocompatibility and cytotoxicity levels remain crucial issues. Gadolinium NPs (GdNPs), have presented high biocompatibility, low cytotoxicity, and excellent hemocompatibility, and have been utilized in MRI-guided radiotherapy, photodynamic and photothermal therapy, etc. Τhe utilization of gadolinium bound to AuNPs may be a promising alternative that would reduce phenomena, such as toxicity, aggregation, etc., and could create a multimodal in vivo contrast and therapeutic agent. This review highlights multi-functionalization strategies against cancer where gold and gadolinium NPs are implicated. Their experimental applications and limitations of the past 5 years will be analyzed in the hope of enlightening the benefits and drawbacks of their proper combination.