Endoscopic ultrasound (EUS)-guided tissue sampling includes the techniques of fine needle aspiration (FNA) and fine needle biopsy (FNB), and both procedures have revolutionized specimen collection from the gastrointestinal tract, especially from remote/inaccessible organs. EUS-FNB has replaced FNA as the procedure of choice for tissue acquisition in solid pancreatic lesions (SPLs) across various society guidelines. FNB specimens provide a larger histological tissue core (preserving tissue architecture) with fewer needle passes, and this is extremely relevant in today’s era of precision and personalized molecular medicine. Innovations in needle tip design are constantly under development to maximize diagnostic accuracy by enhancing histological sampling capabilities. But, apart from the basic framework of the needle, various other factors play a role that influence diagnostic outcomes, namely, sampling techniques (fanning, aspiration or suction, and number of passes), collection methods, on-site evaluation (rapid, macroscopic, or visual), and specimen processing. The choice taken depends strongly on the endoscopist’s preference, available resources at the disposal, and procedure objectives. Hence, in this review, we explicate in detail the concepts and available literature at our disposal on the topic of EUS-guided pancreatic tissue sampling to best guide any practicing gastroenterologist/endoscopist in a not-to-ideal set-up, which EUS-guided tissue acquisition technique is the “best” for their case to augment their diagnostic outcomes.