We present the design and performance of the newly developed PHAROS-a high-resolution, multifunctional PET system integrating time-of-flight (TOF) and depth-of-interaction (DOI) technologies-and report its first-in-human imaging results for brain and breast applications in multiple patient positions. Methods: The PHAROS system features a movable detector head, transformable patient table, and compact footprint, enabling both seated and supine neuroimaging as well as breast and extremity imaging. The scanner's PET ring comprises 20 detector sectors, each with 3 × 12 block detectors in the evaluated 3-detector-module-ring configuration, providing a 19.6-cm axial field of view. Each block detector consists of 8 × 8 lutetium oxyorthosilicate crystals (1.92 × 1.92 × 15 mm3) coupled to dual 4 × 4 silicon photomultiplier arrays for DOI readout. System performance was assessed using a 3-dimensional Hoffman brain phantom and first-in-human studies, including [18F]FDG brain imaging, [18F]florbetaben amyloid PET, [18F]FP-CIT dopamine transporter PET, and prone-position [18F]FDG breast imaging. All images were reconstructed with 3-dimensional ordered-subset expectation maximization incorporating TOF and DOI information. Results: In the Hoffman phantom, cortical and subcortical structures were sharply visualized without artifacts, and layered activity patterns were clearly resolved in coronal and sagittal planes. In the [18F]FDG brain PET of a healthy volunteer, PHAROS produced high-quality images with well-defined cortical and subcortical uptake patterns and clear gray-white matter contrast. In [18F]florbetaben amyloid PET, the amyloid-negative case showed marked gray-white matter contrast and a characteristic spiculated pattern of white matter tracts, whereas the amyloid-positive case exhibited diffuse cortical binding of radiotracer with the relative sparing of the precentral, postcentral, and occipital cortices. Dopamine transporter PET showed reduced bilateral putaminal binding in a patient with Parkinson disease. In prone breast PET, multiple hypermetabolic masses and skin invasion were clearly delineated with high tumor-to-background contrast, also enabling detailed visualization of tumor heterogeneity. Conclusion: These first-in-human results demonstrate that the PHAROS system achieves remarkable spatial resolution and high image quality across diverse applications. Its versatile design, incorporating DOI and TOF technologies, supports a wide range of clinical and research uses, enabling accurate lesion characterization in both neurologic and oncologic settings.