Because of significant differences in institutional contexts, health technology assessment (HTA) systems that are in place in core pharmaceutical markets may not be suitable, fully or in part, for middle-income countries (MICs) and for other noncore markets. Particular challenges may arise when systems based on the economic evaluation paradigm are conceptualized and implemented in MICs, sometimes with an insufficient level of awareness of the local institutional factors that influence pricing and reimbursement decision making. Focusing on pharmaceuticals, this article investigates possible development directions for HTA systems in MICs and noncore markets bearing similar institutional characteristics, and it provides recommendations for a balanced assessment system (BAS). For this, the main paradigms of HTA have also been reviewed briefly and factors influencing HTA and pricing and reimbursement decisions in MICs and in similar noncore countries have been summarized. The proposed BAS framework takes into account available resources and capabilities and is supposed to facilitate access to new pharmaceuticals while ensuring the transparency of decision-making processes and the stability of the pharmaceutical budget.