Technological innovation, cost effectiveness, and miniaturization are key factors that determine the commercial adaptability and sustainability of sensing platforms. Nanoplasmonic biosensors based on nanocup or nanohole arrays are attractive for the development of various miniaturized devices for clinical diagnostics, health management, and environmental monitoring. In this review, we discuss the latest trends in the engineering and development of nanoplasmonic sensors as biodiagnostic tools for the highly sensitive detection of chemical and biological analytes. We focused on studies that have explored flexible nanosurface plasmon resonance systems using a sample and scalable detection approach in an effort to highlight multiplexed measurements and portable point-of-care applications.