Microneedles (MNs) have drawn rising attention owing to their merits of convenience, noninvasiveness, flexible applicability, painless microchannels with boosted metabolism, and precisely tailored multifunction control. MNs can be modified to serve as novel transdermal drug delivery, which conventionally confront with the penetration barrier caused by skin stratum corneum. The micrometer-sized needles create channels through stratum corneum, enabling efficient drug delivery to the dermis for gratifying efficacy. Then, incorporating photosensitizer or photothermal agents into MNs can conduct photodynamic or photothermal therapy, respectively. Besides, health monitoring and medical detection by MN sensors can extract information from skin interstitial fluid and other biochemical/electronic signals. Here, this review discloses a novel monitoring, diagnostic, and therapeutic pattern by MNs, with elaborate discussion about the classified formation of MNs together with various applications and inherent mechanism. Hereby, multifunction development and outlook from biomedical/nanotechnology/photoelectric/devices/informatics to multidisciplinary applications are provided. Programmable intelligent MNs enable logic encoding of diverse monitoring and treatment pathways to extract signals, optimize the therapy efficacy, real-time monitoring, remote control, and drug screening, and take instant treatment.