Surface-enhanced Raman scattering (SERS) has evolved into a powerful analytical measurement technique with the potential for single molecule detection. The technological advancement of handheld Raman instrumentation is powering the development of SERS applications in a variety of industries. Moreover, it is driving the movement from laboratory-based analyses to on-site/remote analyses. As a result, a main research component from this movement is to develop compatible SERS substrates. While the market is dominated by solid-based substrates, solution-based substrates do offer some benefits. These could include low production costs, high scalability, competitive reproducibility and shorter analysis times. The primary focus of the work in this thesis is to develop solution-based SERS substrates and explore their usage for in-solution measurements. This work highlights the development of three different types of solution-based substrates. The first substrate involves the synthesis and optimization of gold nanostars as a colloidal SERS substrate. The SERS performance is investigated and optimized using different Good's buffers, examining the buffer to gold salt concentration ratio and the use of an aggregating agent. In short, the results indicated that gold nanostars with smaller branches provided larger enhancement than those with larger branches, and this has been attributed to the Raman probe surface coverage on the nanostars rather than an electromagnetic effect. A SERS assay is also developed to quantitate methimazole in urine using a handheld Raman spectrometer. The second and third solution-based substrates are metal decorated cellulose nanofibers, also known as plasmonic cellulose nanofibers. These chapters focus on the growth of silver and gold nanoparticles onto oxidized cellulose nanofibers, and are used as a water dispersible substrate. In the development of plasmonic cellulose nanofibers, the cellulose nanofibers have two important roles: (1) to act as a dispersant in water and (2) act as a support for metallic nanoparticles. For both substrates, centrifugation played a key role in producing significant signal enhancement. Cellulose nanofibers decorated with silver nanoparticles were used for in-solution measurements of malachite green, while cellulose nanofibers decorated with gold nanoparticles were used for in-solution measurements of methimazole. Moreover, an assay is developed to quantitate methimazole in synthetic urine with cellulose nanofibers decorated with gold nanoparticles. Measurements using plasmonic cellulose nanofibers are taken with a Raman microscope, however, examples are shown to highlight the capability of remote analysis by coupling the substrates with a handheld Raman spectrometer. This work concludes with a comparative study between solid- and solution-based substrates. Using cellulose nanofibers decorated with gold nanoparticles, membrane- and glass- based SERS substrate are developed. This work discusses the benefits and challenges of solid- and solution-based substrates in terms of substrate development, measurement versatility and reproducibility. The primary contribution of this work is the development of multiple solution-based SERS substrates for in-solution measurements.