Cancer is one of the leading causes of death worldwide. Conventional therapies lack selectivity and suffer from toxicity and drug resistance, leading to metastasis. To overcome these limitations, a new category of nanomaterials exploiting the tumor characteristics has been developed in cancer nanotherapeutics. Among them, pH, metabolism, and the disrupted architecture of cells can be exploited for theranostic applications. Such nanomaterials can be inorganic nanoparticles with silver ones and gain high attention as diagnostic, therapeutic, and antibacterial compounds. Silver has been linked with triggering the death of cancer cells via DNA damage due to the production of reactive oxygen species (ROS) during photodynamic therapy. Thus, improvement of biocompatibility, modification with targeted agents, and drug conjugation promote the use of silver nanoparticles. In this work, we managed to synthesize hybrid Ag@SiO2 core-shell nanoparticles via a modified sol-gel method by tackling the known etching of silver caused by ammonia by employing different bases of the sol-gel reaction. The bases used in the synthetic route were diethylamine (DEA) and triethylamine (TEA) and were monitored with silver nanoparticles individually from the absorbance peak of silver in the UV-vis region, showing no etching of silver in contrast with ammonia, which is usually used in the sol-gel method. Furthermore, we synthesized biocompatible nanoparticles with anticancer and diagnostic properties toward breast cancer cells and glioblastoma cells. The nanoparticles were characterized both structurally and morphologically. Their biological evaluation suggests minor toxicity toward healthy cells and red blood cells (RBCs). Also, the diagnostic potential of the hybrid nanoparticles was exploited by optical fluorescence microscopy. Therefore, we strongly suggest the investigation of such nanostructures as a dual platform for the diagnosis and therapy of cancer.