Thrombosis is characterized by the formation of in vivo blood clots that are localized within arterial or venous blood vessels. These thrombi form beyond the need for physiologically healthy hemostatic responses and can lead to significant medical issues for affected individuals. Unfortunately, the existing standard-of-care therapies for treating thrombosis are systemic in their therapeutic design; therefore, they interfere with the patient's physiological hemostasis. Examples of the severe clinical side effects commonly associated with currently available therapies include, but are not limited to, bleeding complications. Therefore, there is a profound demand for novel therapeutic interventions that can circumvent these debilitating complications, while offering improved therapeutic efficacy. Recent advancements in nanotechnology present an opportunity to develop novel and improved drug delivery systems to meet this clinical demand. Preclinical investigations have begun to uncover the potential of nanotechnology, particularly in the treatment of thrombosis and also in nonhemostatic cardiovascular diseases. This article reviews recent preclinical studies aimed at developing a diverse array of different nanotechnologies for treating thrombosis as well as heart diseases. This review will also outline the limitations with current nanotechnologies and what challenges need to be overcome to translate these novel therapies to the clinic.