This dissertation investigates the feasibility of using capacitive micromachined ultrasonic transducers (CMUTs) for transcranial focused ultrasound (tFUS) in combination with microbubble (MB)-assisted therapy. While tFUS with MBs enables targeted drug delivery across the blood-brain barrier (BBB), safe and efficient clinical translation requires accurate modeling of skull transmission and thermal effects to ensure safe ultrasound delivery, sufficient acoustic pressure output to activate MBs, and broadband detection to monitor MB dynamics. To address these needs, we first introduce a figure of merit for evaluating ultrasound transmission based on coupled elastic-thermal analysis, integrating a micro-CT-derived skull model with ultrasound transmission experiments through skull samples to identify the optimal incidence angle range. Subsequently, focusing on tFUS system development, we perform electrical and acoustic characterization of a single CMUT element and mitigate device nonlinearity via polyphase modulation (PM) to isolate MB emissions during BBB opening. Finally, we demonstrate array-level integration and BBB opening in a rat model using a CMUT transmit-and-receive tFUS array and assess outcomes with PM-based harmonic tracking (and confirmatory MRI). Collectively, these results establish a foundation for human-scale CMUT-based tFUS platforms capable of delivering therapy while simultaneously monitoring MB activity in real time.