pH is considered one of the paramount factors in bodily functions, because most of the cellular tasks exclusively rely on precise pH values. The regulation of pH is a necessary feature of the intracellular atmosphere and can be established as a strong indicator to judge a physiological abnormality in most of the cases. In this context, the current techniques for pH sensing provide us with the futuristic insight to further design therapeutic and diagnostic tools. Thus, pH-sensing (electrochemically and optically) is rapidly evolving toward exciting new applications and expanding researchers’ interests in many chemical contexts, especially in biomedical applications. The adaptation of cutting-edge technology is subsequently producing the modest form of these biosensors as wearable devices, which are providing us the opportunity to target the real-time collection of vital parameters, including pH for improved healthcare systems. The motif of this review is to provide an insight of trending tech-based systems employed in real time or in-vivo pH responsive monitoring. Herein, we briefly go through the pH regulation in the human body to help the beginners and scientific community with quick background knowledge, recent advances in the field, and pH detection in cancerous environments. In the end, we summarize our review by providing an outlook; challenges that need to be addressed and prospective integration of various pH in vivo platforms with modern electronics that can open new avenues of cutting-edge techniques for disease diagnostics and prevention.