The Sherlock Cloud platform at the San Diego Supercomputer Center (SDSC) has been deploying solutions to support critical applications including, but not limited to, cancer research, decoding human immune system, detecting and preventing medical fraud, enterprise risk management and medical device data management. These applications have relied on technologies ranging from the traditional data warehouse to the more recent big data platforms leveraging Hadoop, Software as a Service (SaaS) capability leveraging container technology, business intelligence and analytics solutions and IOT/streaming solutions. Operating these applications and the underlying platforms requires organizations to be agile and visionary in this arena to grow with the ever-changing technological, regulatory and unique customer requirements, while simultaneously ensuring data security and privacy. As such, during our presentation, we will speak to some key aspects of hosting these applications, data and technology platforms within the highly secure and HIPAA-compliant boundaries of our hybrid cloud that spans an on-premise cloud running at UC San Diego, and another operating in AWS Cloud. We will further identify the challenges and lessons learned from deploying, and operating these capabilities across a hybrid cloud setup.